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1.
Cochrane Database Syst Rev ; 10: CD001892, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118160

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is defined as reduced function of the kidneys present for 3 months or longer with adverse implications for health and survival. For several decades low protein diets have been proposed for participants with CKD with the aim of slowing the progression to end-stage kidney disease (ESKD) and delaying the onset of renal replacement therapy. However the relative benefits and harms of dietary protein restriction for preventing progression of CKD have not been resolved. This is an update of a systematic review first published in 2000 and updated in 2006, 2009 and 2018. OBJECTIVES: To determine the efficacy of low protein diets in preventing the natural progression of CKD towards ESKD and in delaying the need for commencing dialysis treatment in non-diabetic adults. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 7 September 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi RCTs in which adults with non-diabetic CKD (stages 3 to 5) not on dialysis were randomised to receive a very low protein intake (0.3 to 0.4 g/kg/day) compared with a low protein intake (0.5 to 0.6 g/kg/day) or a low protein intake compared with a normal protein intake (≥ 0.8 g/kg/day) for 12 months or more. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and extracted data. For dichotomous outcomes (death, all causes), requirement for dialysis, adverse effects) the risk ratios (RR) with 95% confidence intervals (CI) were calculated and summary statistics estimated using the random effects model. Where continuous scales of measurement were used (glomerular filtration rate (GFR), weight), these data were analysed as the mean difference (MD) or standardised mean difference (SMD) if different scales had been used. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: We identified 17 studies with 2996 analysed participants (range 19 to 840). Four larger multicentre studies were subdivided according to interventions so that the review included 21 separate data sets. Mean duration of participant follow-up ranged from 12 to 50 months. Random sequence generation and allocation concealment were considered at low risk of bias in eleven and nine studies respectively. All studies were considered at high risk for performance bias as they were open-label studies. We assessed detection bias for outcome assessment for GFR and ESKD separately. As GFR measurement was a laboratory outcome all studies were assessed at low risk of detection bias. For ESKD, nine studies were at low risk of detection bias as the need to commence dialysis was determined by personnel independent of the study investigators. Five studies were assessed at high risk of attrition bias with eleven studies at low risk. Ten studies were at high risk for reporting bias as they did not include data which could be included in a meta-analysis. Eight studies reported funding from government bodies while the remainder did not report on funding. Ten studies compared a low protein diet with a normal protein diet in participants with CKD categories 3a and b (9 studies) or 4 (one study). There was probably little or no difference in the numbers of participants who died (5 studies 1680 participants: RR 0.77, 95% CI 0.51 to 1.18; 13 fewer deaths per 1000; moderate certainty evidence). A low protein diet may make little or no difference in the number of participants who reached ESKD compared with a normal protein diet (6 studies, 1814 participants: RR 1.05, 95% CI 0.73 to 1.53; 7 more per 1000 reached ESKD; low certainty evidence). It remains uncertain whether a low protein diet compared with a normal protein intake impacts on the outcome of final or change in GFR (8 studies, 1680 participants: SMD -0.18, 95% CI -0.75 to 0.38; very low certainty evidence). Eight studies compared a very low protein diet with a low protein diet and two studies compared a very low protein diet with a normal protein diet. A very low protein intake compared with a low protein intake probably made little or no difference to death (6 studies, 681 participants: RR 1.26, 95% CI 0.62 to 2.54; 10 more deaths per 1000; moderate certainty evidence). However it probably reduces the number who reach ESKD (10 studies, 1010 participants: RR 0.65, 95% CI 0.49 to 0.85; 165 per 1000 fewer reached ESKD; moderate certainty evidence). It remains uncertain whether a very low protein diet compared with a low or normal protein intake influences the final or change in GFR (6 studies, 456 participants: SMD 0.12, 95% CI -0.27 to 0.52; very low certainty evidence). Final body weight was reported in only three studies. It is uncertain whether the intervention alters final body weight (3 studies, 89 participants: MD -0.40 kg, 95% CI -6.33 to 5.52; very low certainty evidence).Twelve studies reported no evidence of protein energy wasting (malnutrition) in their study participants while three studies reported small numbers of participants in each group with protein energy wasting. Most studies reported that adherence to diet was satisfactory. Quality of life was not formally assessed in any studies. AUTHORS' CONCLUSIONS: This review found that very low protein diets probably reduce the number of people with CKD 4 or 5, who progress to ESKD. In contrast low protein diets may make little difference to the number of people who progress to ESKD. Low or very low protein diets probably do not influence death. However there are limited data on adverse effects such as weight differences and protein energy wasting. There are no data on whether quality of life is impacted by difficulties in adhering to protein restriction. Studies evaluating the adverse effects and the impact on quality of life of dietary protein restriction are required before these dietary approaches can be recommended for widespread use.


Assuntos
Dieta com Restrição de Proteínas , Progressão da Doença , Falência Renal Crônica/dietoterapia , Falência Renal Crônica/prevenção & controle , Adulto , Viés , Causas de Morte , Doença Crônica , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Urol ; 204(6): 1320-1325, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32614253

RESUMO

PURPOSE: We evaluated the effect of long-term low dose antibiotic prophylaxis on children's gut microbiota. MATERIALS AND METHODS: We conducted 16S ribosomal RNA gene sequencing using stool samples from 35 patients younger than 3 years old (median age 5.2 months; male-to-female ratio 17:18) who underwent antibiotic treatment during the acute phase of febrile urinary tract infection. Samples were collected at 5 time points, ie before, during and at 1 to 2, 3 to 4, and 5 to 6 months after febrile urinary tract infection onset and antibiotic treatment. Continuous antibiotic prophylaxis using trimethoprim-sulfamethoxazole was initiated in 23 patients with grade III or higher vesicoureteral reflux and was not administered in 12 patients without reflux. RESULTS: Within 2 weeks after initiation of treatment for febrile urinary tract infection almost all enteric bacteria belonged to the order Lactobacillales, and gut microbiota diversity decreased compared to the pretreatment level (average Shannon index 2.9 before treatment, 1.4 during treatment). The diversity recovered within 1 to 2 months after febrile urinary tract infection onset in both groups. Diversity was maintained during the study period in both groups (p=0.43). A smaller proportion of gut microbiota component belonged to the order Enterobacteriales (p=0.002) in the antibiotic prophylaxis group. CONCLUSIONS: Our results revealed that patients receiving continuous antibiotic prophylaxis had normal gut microbiota diversity, indicating that the effect of trimethoprim-sulfamethoxazole on gut microbiota was insignificant. Furthermore, prophylaxis with trimethoprim-sulfamethoxazole might selectively suppress the growth of bacteria belonging to the order Enterobacteriales, such as Escherichia coli and Klebsiella species, which are the main causative bacteria of febrile urinary tract infections.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/efeitos adversos , Disbiose/diagnóstico , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Refluxo Vesicoureteral/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/métodos , Bactérias/genética , Bactérias/isolamento & purificação , Pré-Escolar , DNA Bacteriano/isolamento & purificação , Relação Dose-Resposta a Droga , Esquema de Medicação , Disbiose/induzido quimicamente , Disbiose/epidemiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Lactente , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Masculino , RNA Ribossômico 16S/genética , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Urinárias/complicações , Refluxo Vesicoureteral/diagnóstico , Refluxo Vesicoureteral/etiologia
3.
Arterioscler Thromb Vasc Biol ; 40(8): 1942-1951, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32493170

RESUMO

OBJECTIVE: Vascular calcification contributes to the cause of cardiovascular disease. The calciprotein particle maturation time (T50) in serum, a measure of calcification propensity, has been linked with adverse outcomes in patients with chronic kidney disease, but its role in the general population is unclear. We investigated whether serum T50 is associated with cardiovascular mortality in a large general population-based cohort. Approach and Results: The relationship between serum T50 and cardiovascular mortality was studied in 6231 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) cohort. All-cause mortality was the secondary outcome. Mean (±SD) age was 53±12 years, 50% were male, and mean serum T50 was 329±58 minutes. A shorter serum T50 is indicative of a higher calcification propensity. Serum T50 was inversely associated with circulating phosphate, age, estimated glomerular filtration rate, and alcohol consumption, whereas plasma magnesium was positively associated with serum T50 (P<0.001, total multivariable model R2=0.281). During median (interquartile range) follow-up for 8.3 (7.8-8.9) years, 364 patients died (5.8%), of whom 95 (26.1%) died from a cardiovascular cause. In multivariable Cox proportional hazard models, each 60 minutes decrease in serum T50 was independently associated with a higher risk of cardiovascular mortality (fully adjusted hazard ratio [95% CI], 1.22 [1.04-1.36], P=0.021). This association was modified by diabetes mellitus; stratified analysis indicated a more pronounced association in individuals with diabetes mellitus. CONCLUSIONS: Serum T50 is independently associated with an increased risk of cardiovascular mortality in the general population and thus may be an early and potentially modifiable risk marker for cardiovascular mortality.


Assuntos
Doenças Cardiovasculares/etiologia , Calcificação Vascular/sangue , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Humanos , Falência Renal Crônica/prevenção & controle , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco
4.
Medicine (Baltimore) ; 99(21): e20234, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481298

RESUMO

BACKGROUND: The prevalence of chronic kidney disease (CKD) has been rapidly increasing and has become one of the most concerned global health problems. It is of good importance to improve therapeutic efficiency of CKD and delay disease progression to end stage renal disease (ESRD). Traditional Chinese Medicine (TCM) is a widely used complementary therapy for patients with CKD. The aim of this study is to evaluate whether basic treatment combined with Chinese herbs mixture Qi Gui Yi Shen decoction could achieve better therapeutic effect on CKD patients. METHODS: To determine whether traditional Chinese medicine Qi Gui Yi Shen decoction could achieve better therapeutic effect, we will conduct a randomized controlled trial. A total of 100 CKD patients that meet the inclusion criteria will be enrolled and divided into 2 groups: Qi Gui Yi Shen group (QGYS group) and placebo group. Each group will receive 6-monthly basic treatment in combination with TCM or placebo 3 times per day. Efficacy of Qi Gui Yi Shen decoction is evaluated by analyzing renal function and TCM symptoms, other efficacy assessments include serum level of PAI-I, expression of transforming growth factor beta1 (TGF-beta1). Routine blood count, plasma albumin (ALB), and alanine transaminase (ALT) are evaluated as side effect and safety profile. DISCUSSION: The results from the clinical trial will provide evidence for the effectiveness and safety of Qi Gui Yi Shen Decoction as a treatment for CKD patients. Furthermore, this will propose a new theory and method for CKD treatment. TRIAL REGISTRATION: Registered with Chinese Clinical Trials Registry at www.chictr.org. (Registration number: ChiCTR1900021622) on 1 March 2019.


Assuntos
Terapia Combinada/métodos , Medicina Tradicional Chinesa/métodos , Insuficiência Renal Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/prevenção & controle , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Segurança , Albumina Sérica/análise , Fator de Crescimento Transformador beta1/sangue , Adulto Jovem
5.
Nat Rev Rheumatol ; 16(5): 255-267, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32203285

RESUMO

Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus that can lead to irreversible renal impairment. Although the prognosis of LN has improved substantially over the past 50 years, outcomes have plateaued in the USA in the past 20 years as immunosuppressive therapies have failed to reverse disease in more than half of treated patients. This failure might reflect disease complexity and heterogeneity, as well as social and economic barriers to health-care access that can delay intervention until after damage has already occurred. LN progression is still poorly understood and involves multiple cell types and both immune and non-immune mechanisms. Single-cell analysis of intrinsic renal cells and infiltrating cells from patients with LN is a new approach that will help to define the pathways of renal injury at a cellular level. Although many new immune-modulating therapies are being tested in the clinic, the development of therapies to improve regeneration of the injured kidney and to prevent fibrosis requires a better understanding of the mechanisms of LN progression. This mechanistic understanding, together with the development of clinical measures to evaluate risk and detect early disease and better access to expert health-care providers, should improve outcomes for patients with LN.


Assuntos
Rim/citologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/complicações , Biomarcadores/análise , Ensaios Clínicos como Assunto , Progressão da Doença , Diagnóstico Precoce , Fibrose/prevenção & controle , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Imunossupressores/uso terapêutico , Rim/lesões , Rim/metabolismo , Rim/patologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/prevenção & controle , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/genética , Nefrite Lúpica/imunologia , Prognóstico , Regeneração/efeitos dos fármacos , Regeneração/fisiologia , Fatores Socioeconômicos , Estados Unidos/epidemiologia
6.
Cochrane Database Syst Rev ; 3: CD003965, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162319

RESUMO

BACKGROUND: IgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10 years and in 30% to 40% of patients within 20 years from the onset of disease. This is an update of a Cochrane review first published in 2003 and updated in 2015. OBJECTIVES: To determine the benefits and harms of immunosuppression strategies for the treatment of IgA nephropathy. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 9 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of treatment for IgA nephropathy in adults and children and that compared immunosuppressive agents with placebo, no treatment, or other immunosuppressive or non-immunosuppressive agents. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study risk of bias and extracted data. Estimates of treatment effect were summarised using random effects meta-analysis. Treatment effects were expressed as relative risk (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Risks of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE methodology. MAIN RESULTS: Fifty-eight studies involving 3933 randomised participants were included. Six studies involving children were eligible. Disease characteristics (kidney function and level of proteinuria) were heterogeneous across studies. Studies evaluating steroid therapy generally included patients with protein excretion of 1 g/day or more. Risk of bias within the included studies was generally high or unclear for many of the assessed methodological domains. In patients with IgA nephropathy and proteinuria > 1 g/day, steroid therapy given for generally two to four months with a tapering course probably prevents the progression to ESKD compared to placebo or standard care (8 studies; 741 participants: RR 0.39, 95% CI 0.23 to 0.65; moderate certainty evidence). Steroid therapy may induce complete remission (4 studies, 305 participants: RR 1.76, 95% CI 1.03 to 3.01; low certainty evidence), prevent doubling of serum creatinine (SCr) (7 studies, 404 participants: RR 0.43, 95% CI 0.29 to 0.65; low certainty evidence), and may lower urinary protein excretion (10 studies, 705 participants: MD -0.58 g/24 h, 95% CI -0.84 to -0.33;low certainty evidence). Steroid therapy had uncertain effects on glomerular filtration rate (GFR), death, infection and malignancy. The risk of adverse events with steroid therapy was uncertain due to heterogeneity in the type of steroid treatment used and the rarity of events. Cytotoxic agents (azathioprine (AZA) or cyclophosphamide (CPA) alone or with concomitant steroid therapy had uncertain effects on ESKD (7 studies, 463 participants: RR 0.63, 95% CI 0.33 to 1.20; low certainty evidence), complete remission (5 studies; 381 participants: RR 1.47, 95% CI 0.94 to 2.30; very low certainty evidence), GFR (any measure), and protein excretion. Doubling of serum creatinine was not reported. Mycophenolate mofetil (MMF) had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, infection, and malignancy. Death was not reported. Calcineurin inhibitors compared with placebo or standard care had uncertain effects on complete remission, SCr, GFR, protein excretion, infection, and malignancy. ESKD and death were not reported. Mizoribine administered with renin-angiotensin system inhibitor treatment had uncertain effects on progression to ESKD, complete remission, GFR, protein excretion, infection, and malignancy. Death and SCr were not reported. Leflunomide followed by a tapering course with oral prednisone compared to prednisone had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, and infection. Death and malignancy were not reported. Effects of other immunosuppressive regimens (including steroid plus non-immunosuppressive agents or mTOR inhibitors) were inconclusive primarily due to insufficient data from the individual studies in low or very low certainty evidence. The effects of treatments on death, malignancy, reduction in GFR at least of 25% and adverse events were very uncertain. Subgroup analyses to determine the impact of specific patient characteristics such as ethnicity or disease severity on treatment effectiveness were not possible. AUTHORS' CONCLUSIONS: In moderate certainty evidence, corticosteroid therapy probably prevents decline in GFR or doubling of SCr in adults and children with IgA nephropathy and proteinuria. Evidence for treatment effects of immunosuppressive agents on death, infection, and malignancy is generally sparse or low-quality. Steroid therapy has uncertain adverse effects due to a paucity of studies. Available studies are few, small, have high risk of bias and generally do not systematically identify treatment-related harms. Subgroup analyses to identify specific patient characteristics that might predict better response to therapy were not possible due to a lack of studies. There is no evidence that other immunosuppressive agents including CPA, AZA, or MMF improve clinical outcomes in IgA nephropathy.


Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Esteroides/uso terapêutico , Adulto , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Causas de Morte , Criança , Intervalos de Confiança , Creatinina/sangue , Esquema de Medicação , Quimioterapia Combinada , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/prevenção & controle , Falência Renal Crônica/terapia , Leflunomida/efeitos adversos , Leflunomida/uso terapêutico , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Proteinúria/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Ribonucleosídeos/efeitos adversos , Ribonucleosídeos/uso terapêutico , Risco , Esteroides/administração & dosagem , Esteroides/efeitos adversos
7.
Rev Med Suisse ; 16(683): 412-416, 2020 Feb 26.
Artigo em Francês | MEDLINE | ID: mdl-32129019

RESUMO

Over the last decades, an increasing number of cases of chronic and end-stage kidney disease has been observed in Central America and Asia. This kidney disease mainly affects young farmers without classic renal risk factors. The clinical presentation includes a progressive decrease of the glomerular filtration rate, minimal proteinuria and the presence of tubulo-interstitial nephritis at renal biopsy. A close link with global warming is suspected for this disease, called (according to its location) meso-american nephropathy, Sri Lanka nephropathy or chronic kidney disease of unknown etiology. Others have suggested that intake of water contaminated with pesticides may be responsible. This article provides an overview of this new kidney disease. Measures to prevent acute kidney injury during heat waves in Switzerland are also discussed.


Assuntos
Aquecimento Global , Nefropatias/epidemiologia , Nefropatias/etiologia , Rim/patologia , Rim/fisiopatologia , América Central/epidemiologia , Humanos , Nefropatias/prevenção & controle , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Sri Lanka/epidemiologia , Suíça/epidemiologia
8.
PLoS One ; 15(2): e0227719, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32012159

RESUMO

BACKGROUND: On-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD. MATERIALS AND METHODS: We conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays. RESULTS: We immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0-74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80-0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains. CONCLUSIONS: Seroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population. TRIAL REGISTRATION: ClinicalTrial.gov, NCT04122222.


Assuntos
Imunidade Inata , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Falência Renal Crônica/prevenção & controle , Adulto , Idoso , Azotemia/imunologia , Azotemia/patologia , Proliferação de Células/genética , Feminino , Testes de Inibição da Hemaglutinação , Hemodiafiltração , Humanos , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/virologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/virologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Linfócitos T/imunologia , Vacinação , Vacinas/administração & dosagem
9.
Dtsch Med Wochenschr ; 145(4): 223-231, 2020 02.
Artigo em Alemão | MEDLINE | ID: mdl-32069489

RESUMO

Chronic kidney disease (CKD) is an increasing health problem in all societies. The role of diabetes mellitus and hypertension in CKD is well established in the medical community. This is not necessarily the case for the various forms of glomerulonephitis (GN). The single entities of GN are rare diseases. In total, glomerulonephritis, however, is accountable for about 20 % of all patients which reach end stage renal disease (ESRD). GN therefore plays an important clinical role. Since many forms of GN have only sparse clinical symptoms at the beginning of the disease and the treatment is only effective in early stages, it is important for patients' outcome to make an early diagnosis. In case of any - even small - changes in the urine of patients the diagnoses of GN should be considered. It is the purpose of this article to describe the clinical significance and the road to the diagnosis of the most frequent forms of GN to allow an early start of therapy in order to prevent the development of ESRD.


Assuntos
Glomerulonefrite , Glomerulonefrite/classificação , Glomerulonefrite/diagnóstico , Glomerulonefrite/fisiopatologia , Glomerulonefrite/terapia , Humanos , Rim/fisiopatologia , Falência Renal Crônica/prevenção & controle
10.
N Engl J Med ; 382(7): 622-631, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053298

RESUMO

BACKGROUND: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Glucocorticoides/administração & dosagem , Falência Renal Crônica/prevenção & controle , Troca Plasmática , Administração Oral , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Terapia Combinada , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Incidência , Quimioterapia de Indução , Nefropatias/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Troca Plasmática/efeitos adversos , Rituximab/uso terapêutico
11.
Cochrane Database Syst Rev ; 1: CD003232, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31927782

RESUMO

BACKGROUND: Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions involve the use of steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This 2019 publication is an update of a review first published in 2008 and updated in 2015. OBJECTIVES: To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 21 November 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes. MAIN RESULTS: Forty studies (3764 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large international study groups. Induction therapy: Plasma exchange as adjunctive therapy may reduce the need for dialysis at three (2 studies: RR 0.43, 95% CI 0.23 to 0.78; I2 = 0%) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72; I2 = 0%) (low certainty evidence). Plasma exchange may make little or no difference to death, serum creatinine (SCr), sustained remission or to serious or the total number of adverse events. Plasma exchange may increase the number of serious infections (5 studies: RR 1.26, 95% CI 1.03 to 1.54; I2 = 0%; low certainty evidence). Remission rates for pulse versus continuous cyclophosphamide (CPA) were equivalent but pulse treatment may increase the risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87; I2 = 0%) (low certainty evidence) compared with continuous cyclophosphamide. Pulse CPA may make little or no difference to death at final follow-up, or SCr at any time point. More patients required dialysis in the pulse CPA group. Leukopenia was less common with pulse treatment; however, nausea was more common. Rituximab compared to CPA probably makes little or no difference to death, remission, relapse, severe adverse events, serious infections, or severe adverse events. Kidney function and dialysis were not reported. A single study reported no difference in the number of deaths, need for dialysis, or adverse events between mycophenolate mofetil (MMF) and CPA. Remission was reported to improve with MMF however more patients relapsed. A lower dose of steroids was probably as effective as high dose and may be safer, causing fewer infections; kidney function and relapse were not reported. There was little of no difference in death or remission between six and 12 pulses of CPA. There is low certainty evidence that there were less relapses with 12 pulses (2 studies: RR 1.57, 95% CI 0.96 to 2.56; I2 = 0%), but more infections (2 studies: RR 0.79, 95% CI 0.36 to 1.72; I2 = 45%). One study reported severe adverse events were less in patients receiving six compared to 12 pulses of CPA. Kidney function and dialysis were not reported. There is limited evidence from single studies about the effectiveness of intravenous immunoglobulin, avacopan, methotrexate, immunoadsorption, lymphocytapheresis, or etanercept. Maintenance therapy: Azathioprine (AZA) has equivalent efficacy as a maintenance agent to CPA with fewer episodes of leucopenia. MMF resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction and maintenance agent. Oral co-trimoxazole did not reduce relapses in granulomatosis with polyangiitis. There were fewer relapses but more serious adverse events with leflunomide compared to methotrexate. There is limited evidence from single studies about the effectiveness of methotrexate versus CPA or AZA, cyclosporin versus CPA, extended versus standard AZA, and belimumab. AUTHORS' CONCLUSIONS: Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst CPA is standard induction treatment, rituximab and MMF were also effective. AZA, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.


Assuntos
Lesão Renal Aguda/terapia , Nefropatias/terapia , Vasculite/terapia , Adulto , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Glomerulonefrite/complicações , Humanos , Imunossupressores/uso terapêutico , Rim/irrigação sanguínea , Falência Renal Crônica/prevenção & controle , Troca Plasmática , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Clin Exp Nephrol ; 24(1): 73-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605314

RESUMO

BACKGROUND: Crescent formation in immunoglobulin A nephropathy (IgAN) has been demonstrated to be a risk factor for worse outcomes. For IgAN patients with 0-25% crescentic glomeruli (C1), whether corticosteroids (CS) can improve the prognosis remains unclear. We tried to investigate the need for using CS in IgAN patients with C1 in different proteinuria levels. METHODS: A total of 120 eligible IgAN patients with C1 from two academic medical centers were retrospectively studied, and 57 (47.5%) received CS. Patients were grouped according to with or without CS. The outcomes were the rate of estimated glomerular filtration rate (eGFR) decline (ml/min per 1.73 m2/year) and a composite outcome (50% decrease in eGFR, end stage renal disease (ESRD) or death due to kidney disease). The progression of adverse outcome among them were analyzed in Kaplan-Meier curve. The independent significance of CS on renal outcome or eGFR decline rate were analyzed by multivariable Cox regression or linear regression. RESULTS: Unadjusted Kaplan-Meier showed that the outcome of treated patients was better than that of the untreated patients. Multiple Cox regression and linear regression analysis found that CS independently protected the renal outcome and decreased the eGFR decline rate. In the subgroup analysis, multivariate linear regression showed that CS decreased the eGFR decline rate both in proteinuria ≥ 1 g/day and < 1 g/day. CONCLUSIONS: CS protected the renal outcome and slowed the eGFR decline rate of IgAN patients with C1, it also decreased the eGFR decline rate even in those with initial proteinuria < 1 g/day.


Assuntos
Corticosteroides/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite por IGA/tratamento farmacológico , Glomérulos Renais/efeitos dos fármacos , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Proteinúria/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , China , Progressão da Doença , Feminino , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/fisiopatologia , Humanos , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/prevenção & controle , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Glomérulos Renais/fisiopatologia , Masculino , Proteinúria/imunologia , Proteinúria/mortalidade , Proteinúria/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Eur J Pharmacol ; 867: 172844, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31811859

RESUMO

This study tested the hypothesis that the enhancement of glucagon-like peptide-1 (GLP-1) level through either exogenous supply of GLP-1 agonist, liraglutide or prevention of endogenous GLP-1 degradation with dipeptidyl peptidease-4 inhibitor, lingaliptin ameliorates angiotensin II (Ang II)-induced renal fibrosis. Sprague-Dawley rats were randomly divided into four groups: 0.9% saline or Ang II (500 ng/kg/min) was infused with osmotic minipumps for 4 weeks, defined as sham and Ang II groups. In drug treated groups, liraglutide (0.3 mg/kg) was injected subcutaneously twice daily or linagliptin (8 mg/kg) was administered daily via oral gavage during Ang II infusion. Compared with Ang II stimulation, liraglutide or linagliptin comparatively down-regulated the protein level of the AT1 receptor, and up-regulated the AT2 receptor, as identified by a reduced AT1/AT2 ratio (all p < 0.05), consistent with less locally-expressed AT1 receptor and enhanced AT2 receptor in the glomerular capillaries and proximal tubules of the renal cortex. Furthermore, both drugs significantly increased the expression of GLP-1 receptor and attenuated the protein levels of TLR4, NOX4 and IL-6. The populations of macrophages and α-SMA expressing myofibroblasts decreased with treatment of liraglutide and linagliptin, in coincidence with the reduced expression of phosphor-Smad2/3, Smad4, TGFß1, and up-regulated Smad7. Along with these modulations, renal morphology was preserved and synthesis of fibronectin/collagen I was down-regulated, as identified by small collagen-rich area in the renal cortex. These results suggest that the preservation of GLP-1 level using liraglutide or linagliptin might be considered as an add-on therapeutic option for inhibiting Ang II induced renal fibrosis and failure.


Assuntos
Angiotensina II/metabolismo , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Incretinas/administração & dosagem , Falência Renal Crônica/prevenção & controle , Rim/patologia , Angiotensina II/administração & dosagem , Animais , Dipeptidil Peptidase 4/metabolismo , Modelos Animais de Doenças , Fibrose , Peptídeo 1 Semelhante ao Glucagon/agonistas , Humanos , Rim/efeitos dos fármacos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Linagliptina/administração & dosagem , Liraglutida/administração & dosagem , Masculino , Proteólise/efeitos dos fármacos , Ratos
15.
Hemodial Int ; 24(2): 175-181, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31820557

RESUMO

INTRODUCTION: Despite mounting evidence that increased frequency and duration of hemodialysis (HD) improves outcomes, less than 1% of HD patients worldwide receive nocturnal hemodialysis (NHD). Many perceived barriers exist to providing NHD and increasing its provision. METHODS: A retrospective analysis of nocturnal therapy using a low-flow dialysate system in 4 European centers for a minimum of 12 months, with data collected on patient demographics, training times, safety features, medications, and biochemical parameters at baseline and at 6 and 12 months. FINDINGS: Data were collected on 21 patients, with 12-month analysis available for 20 patients. Mean dialysis duration was 28 hours per week, with most dialysis on an alternate night regimen using 50-60 L of dialysate per session. All vascular access types were represented, and low molecular weight heparin was used as a bolus. All biochemical parameters met European standards, with a trend for improvement in standardized Kt/V, phosphate, hemoglobin, and albumin. There was a significant reduction in phosphate binder usage and a reduction in blood pressure medication. Training time was 9.6 sessions for independence at home, with 2 additional sessions to transition to NHD. Additional safety features included an alarmed drip tray under the cycler and moisture sensors under the venous needle (all patients used dual-cannulation technique). No patient safety events were reported. DISCUSSION: These data support the use of a low-flow dialysate system for provision of NHD at home. Biochemical parameters were good, medication burden was reduced at 12 months, and all patients received more than double the duration of HD provided in standard in-center units. While patient numbers were small, low-flow dialysis in this cohort was both effective and safe. Use of this alternative HD system could reduce some of the barriers to NHD, increasing the uptake of therapy in Europe, and improving long-term patient outcomes.


Assuntos
Soluções para Diálise/metabolismo , Hemodiálise no Domicílio/métodos , Falência Renal Crônica/prevenção & controle , Falência Renal Crônica/terapia , Adulto , Idoso , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J. bras. nefrol ; 41(4): 509-517, Out.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056618

RESUMO

Abstract Introduction: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. Methods: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. Results: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. Conclusion: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.


Resumo Introdução: Embora a microalbuminúria continue sendo o padrão ouro para a detecção precoce da nefropatia diabética (ND), ela não é um preditor suficientemente preciso do risco de ND. Assim, novos biomarcadores para prever mais precocemente o risco de ND e possivelmente evitar a ocorrência de doença renal terminal estão sendo investigados. Objetivo: Investigar a zinco-alfa2-glicoproteína (ZAG) como marcador precoce de ND em pacientes com debates mellitus tipo 2 (DM2). Métodos: Os 88 indivíduos incluídos foram divididos em quatro grupos: grupo controle (Grupo I), composto por voluntários saudáveis normais; e três grupos de pacientes com DM2 assim divididos: grupo normoalbuminúria (Grupo II), subdivididos em TFG normal e TFG > 120 mL/min/1,73 m2), grupo microalbuminúria (Grupo III) e grupo macroalbuminúria (Grupo IV). Todos foram submetidos a urinálise e exames para determinar glicemia, HbA1c, função hepática, creatinina sérica, ácido úrico, perfil lipídico, cálculo da TFG, relação albumina/creatinina (RAC) e dosagem urinária e sérica de ZAG. Resultados: Os níveis séricos e urinários de ZAG foram mais elevados nos pacientes com DM2 em comparação aos controles. Foi identificada diferença estatisticamente significativa entre os grupos estudados em relação aos níveis séricos e urinários de ZAG. Os níveis urinários de ZAG foram positivamente correlacionados com a RAC. Ambos os níveis de ZAG foram negativamente correlacionados com TFG. Os níveis urinários de ZAG no subgrupo com TFG ˃ 120 mL/min/1,73m2 foram maiores do que no subgrupo com TFG normal. Conclusão: Constatamos que a ZAG sérica e urinária pode ser um útil biomarcador precoce para detecção de ND em pacientes com DM2, sendo detectável mais precocemente que microalbuminúria.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Biomarcadores/análise , Proteínas de Plasma Seminal/análise , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/fisiopatologia , Estudos de Casos e Controles , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Medição de Risco , Creatinina/sangue , Diagnóstico Precoce , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Nefropatias Diabéticas/sangue , Albuminúria/urina , Taxa de Filtração Glomerular/fisiologia , Falência Renal Crônica/prevenção & controle
18.
Am J Nephrol ; 50(5): 333-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655812

RESUMO

BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet. METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death. CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.


Assuntos
Albuminúria/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Falência Renal Crônica/prevenção & controle , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Naftiridinas/uso terapêutico , Idoso , Albuminúria/etiologia , Albuminúria/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/urina , Progressão da Doença , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/urina , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Resultado do Tratamento
19.
Am J Nephrol ; 50(5): 375-385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600749

RESUMO

BACKGROUND: Markers currently used to predict the likelihood of rapid disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) are expensive and time consuming to assess and often have limited sensitivity. New, easy-to-measure markers are therefore needed that alone or in combination with conventional risk markers can predict the rate of disease progression. In the present study, we investigated the ability of tubular damage and inflammation markers to predict kidney function decline. METHODS: At baseline, albumin, immunoglobulin G, kidney injury molecule 1, ß2 microglobulin (ß2MG), heart-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, and monocyte chemotactic protein-1 -(MCP-1) were measured in 24-h urine samples of patients participating in a study investigating the therapeutic efficacy of lanreotide in ADPKD. Individual change in estimated glomerular filtration rate (eGFR) during follow-up was calculated using mixed-model analysis taking into account 13 -eGFRs (chronic kidney disease EPIdemiology) per patient. Logistic regression analysis was used to select urinary biomarkers that had the best association with rapidly progressive disease. The predictive value of these selected urinary biomarkers was compared to other risk scores using C-statistics. RESULTS: Included were 302 patients of whom 53.3% were female, with an average age of 48 ± 7 years, eGFR of 52 ± 12 mL/min/1.73 m2, and a height-adjusted total kidney volume (htTKV) of 1,082 (736-1,669) mL/m. At baseline, all urinary damage and inflammation markers were associated with baseline eGFR, also after adjustment for age, sex and baseline htTKV. For longitudinal analyses only patients randomized to standard care were considered (n = 152). A stepwise backward analysis revealed that ß2MG and MCP-1 showed the strongest association with rapidly progressive disease. A urinary biomarker score was created by summing the ranking of tertiles of ß2MG and MCP-1 excretion. The predictive value of this urinary biomarker score was higher compared to that of the Mayo htTKV classification (area under the curve [AUC] 0.73 [0.64-0.82] vs. 0.61 [0.51-0.71], p = 0.04) and comparable to that of the predicting renal outcomes in -ADPKD score (AUC 0.73 [0.64-0.82] vs. 0.65 [0.55-0.75], p = 0.18). In a second independent cohort with better kidney function, similar results were found for the urinary biomarker score. CONCLUSION: Measurement of urinary ß2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or PKD mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD.


Assuntos
Falência Renal Crônica/diagnóstico , Peptídeos Cíclicos/uso terapêutico , Rim Policístico Autossômico Dominante/complicações , Somatostatina/análogos & derivados , Adulto , Biomarcadores/urina , Quimiocina CCL2/urina , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Túbulos Renais/imunologia , Túbulos Renais/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/tratamento farmacológico , Rim Policístico Autossômico Dominante/patologia , Rim Policístico Autossômico Dominante/urina , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Somatostatina/uso terapêutico , Fatores de Tempo , Microglobulina beta-2/urina
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