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The incidence of monoclonal gammopathy (MG) increases with age. In individuals over 80 years of age, we can diagnose the presence of monoclonal immunoglobulin (MIg) in up to 10 % of cases. Not only malignant diseases such as multiple myeloma (MM), but also benign forms such as MGUS (monoclonal gammopathy of undetermined significance) can lead to renal involvement. The light chains of immunoglobulins (LC) are the most damaging to the kidneys, as they are freely filtered into the urine due to their molecular weight. Detection of MIg relies mainly on a combination of immunofixation electrophoresis of serum (IELFO) and urine and determination of free light chains (FLC) of kappa and lambda and their ratio (κ/λ) in serum. The combination of these tests will detect the presence of MIg with 99 % sensitivity. Renal damage in MG may be caused by direct deposition of MIg in the glomeruli (e.g. AL amyloidosis, LC deposition disease) or tubules (in the distal tubule as a myeloma kidney or in the proximal tubule as Fanconi syndrome or proximal tubulopathy). Typical urinary findings in these diseases are moderate or severe proteinuria or nephrotic syndrome. Acute kidney injury (AKI) can be expected especially when serum FLC is >500 mg/l. Renal biopsy is crucial to establish an accurate diagnosis and thus initiate the correct treatment. Treatment of these types of renal damage involves the same treatment regimens used in the treatment of MM, including proteasome inhibitors or daratumumab.
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Mieloma Múltiplo , Paraproteinemias , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Paraproteinemias/complicações , Paraproteinemias/diagnóstico , Nefropatias/etiologia , Nefropatias/diagnósticoRESUMO
OBJECTIVES: Rituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug. METHODS: We compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023. The population-pharmacokinetic analysis was based on the rituximab dosing, the patients' characteristics, rituximab levels and anti-rituximab antibodies. RESULTS: The analysis, which was based on data from 185 patients, clearly highlighted differing rituximab dosing requirements for patients with ANCA associated vasculitis and minimal change disease compared to those with membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This corresponded to the good treatment response of the first two diseases and the unreliable efficacy for the others. The model predicts the rituximab pharmacokinetics with high degree of accuracy when body weight, proteinuria, type of glomerulonephritis, treatment length and anti-rituximab antibodies formation are used as covariates. We proposed a dosing schedule with shortened dosing intervals for difficult-to-treat diagnoses with high proteinuria. CONCLUSION: In order to ensure reliable and comparable exposure of rituximab with respect to the full range of glomerular diseases, the dosing schedule should be adjusted for membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This is largely, but not solely, due to the enhanced level of unselective proteinuria in these diseases.
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Rituximab , Rituximab/farmacocinética , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Glomerulonefrite/tratamento farmacológico , Modelos Biológicos , Esquema de Medicação , Adulto Jovem , Resultado do Tratamento , Glomerulonefrite Membranosa/tratamento farmacológico , Relação Dose-Resposta a DrogaRESUMO
INTRODUCTION: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN. METHODS: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records. RESULTS: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) µmol/L in the conservatively managed group versus 374 (249-558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001). CONCLUSIONS: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.
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Nefrite Intersticial , Diálise Renal , Humanos , Estudos Retrospectivos , Creatinina , República Tcheca , Diálise Renal/efeitos adversos , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/diagnóstico , Corticosteroides/uso terapêutico , Rim/patologiaRESUMO
Background: Activity and chronicity of kidney involvement in ANCA-associated vasculitis (AAV) can be currently reliably evaluated only by kidney biopsy. In this study, we measured a panel of serum and urinary biomarkers collected at the time of kidney biopsy and hypothesized that they could reflect specific histopathological parameters in the biopsy and help to predict prognosis. Methods: We examined a cohort of 45 patients with AAV and 10 healthy controls. Biomarker levels (DKK-3, CD163, EGF, PRO-C6 and C3M) were measured in this study by ELISA. Biopsies were scored with a scoring system for AAV (focal x crescentic x sclerotic x mixed class) and interstitial fibrosis was quantified. Results: Levels of urinary DKK-3, CD163, EGF, PRO-C6 and C3M significantly differed among biopsy classes in AAV, with urinary DKK-3 and PRO-C6 levels being highest in the sclerotic class and lowest in the focal class, urinary CD163 levels highest in the crescentic class and urinary C3M levels highest in the focal class. Moreover, the urinary biomarkers were able to discriminate focal biopsy class from the other classes. Urinary DKK-3, EGF, PRO-C6 and C3M levels measured at the time of biopsy were also significantly related to the extent of fibrosis and to the final kidney function at the end of follow-up. Conclusions: This small pilot study suggests that selected urinary biomarkers of fibrosis and inflammation may reflect changes in the kidney biopsy and be prognostic of kidney outcome in patients with AAV.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Fator de Crescimento Epidérmico , Projetos Piloto , Rim/patologia , Inflamação/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Biomarcadores/urina , FibroseRESUMO
Chronic kidney disease (CKD) affects 10% of the population of developed countries and significantly affects the population health. In addition to the well-known renoprotection tools slowing down the progression of CKD, SGLT2 inhibitors have been newly introduced into clinical practice based on the results of extensive studies, both in diabetics and non-diabetics. This expert opinion discusses the classification of CKD, current renoprotection options, and the recent role of SGLT2 inhibitors in the care of patients with CKD.
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Médicos , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Nefrologistas , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Prova Pericial , Insuficiência Renal Crônica/terapiaRESUMO
Anaemia is a very common complication of chronic kidney disease (CKD) and renal failure. The view of the treatment of anaemia has changed considerably since the introduction of ESAs (erythropoiesis-stimulating agents) into clinical practice, and the safety of this treatment is now prioritised over complete normalisation of haemoglobin (Hb) values. Iron administration is the mainstay of treatment in this group of patients, with intravenous administration proving to be both more effective and safer in both predialysis and dialysis patients. In addition to the long-used ESAs, a number of new agents developed to favourably influence erythropoiesis have recently been tested for the correction of anaemia. Among those with the greatest potential are the HIF-stabilizers (roxadustat, molidustat, vadadustat and daprodustat), which act through stimulation of erythropoiesis genes and thus represent a novel mechanism of action in the treatment of anaemia. In phase 3 clinical trials, these agents have shown the same efficacy in increasing Hb levels as ESAs, but much emphasis has recently been placed on their safety profile. They are orally administered agents and some of them are already approved and used in clinical practice. The first of these, roxadustat, is currently reimbursed also in the Czech Republic. Other molecules affecting anaemia, such as sotatercept, have also been confirmed to be effective in phase 1 and 2 clinical trials and are awaiting results from larger randomised trials.
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Anemia , Eritropoetina , Hematínicos , Inibidores de Prolil-Hidrolase , Insuficiência Renal Crônica , Humanos , Inibidores de Prolil-Hidrolase/uso terapêutico , Insuficiência Renal Crônica/complicações , Anemia/tratamento farmacológico , Anemia/etiologia , Hematínicos/uso terapêuticoRESUMO
Atypical hemolytic uremic syndrome (aHUS), also called complement-mediated hemolytic uremic syndrome (CM-HUS), is a rare disease caused by dysregulation in the alternative complement activation pathway. It is a life-threatening condition causing ischemia of a number of organs, and it typically causes acute kidney injury. This disorder may be triggered by various factors including viral or bacterial infections, pregnancy, surgery, and injuries. In about 60% of cases, the genetic origin of the disease can be identified-commonly mutations affecting complementary factor H and MCP protein. Eculizumab, a monoclonal antibody to the C5 component of the complement, represents the current effective treatment.We describe a case of a young woman with a previous history of polyvalent allergies, who developed atypical hemolytic uremic syndrome after vaccination with mRNA vaccine against SARS-CoV-2. The disease manifested by scleral bleeding, acute renal insufficiency, anemia, and thrombocytopenia. The patient was treated with plasma exchanges without sufficient effect; remission occurred only after starting treatment with eculizumab. Genetic examination showed that the patient is a carrier of multiple inherited risk factors (a rare pathogenic variant in CFH, MCPggaac haplotype of the CD46 gene, and the risk haplotype CFH H3). The patient is currently in hematological remission with persistent mild renal insufficiency, continuing treatment with eculizumab/ravulizumab. By this case report, we meant to point out the need for careful monitoring of people after vaccination, as it may trigger immune-mediated diseases, especially in those with predisposing factors.
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Injúria Renal Aguda , Síndrome Hemolítico-Urêmica Atípica , COVID-19 , Feminino , Humanos , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Fator H do Complemento/genética , SARS-CoV-2 , RNA Mensageiro , Vacinas contra COVID-19/efeitos adversos , Proteínas do Sistema Complemento/genética , Injúria Renal Aguda/complicações , Anticorpos Monoclonais , Vacinação/efeitos adversos , Vacinas de mRNARESUMO
Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys being the most commonly and earliest affected organ. Previously described amyloid A amyloidosis is linked to increased production and deposition of serum amyloid A proteins secondary to inflammatory conditions arising from infectious, metabolic, or genetic causes. Here we describe a family with primary amyloid A amyloidosis due to a chr11:18287683 T>C (human genome version19) mutation in the SAA1 promoter linked to the amyloidogenic SAA1.1 haplotype. This condition leads to a doubling of the basal SAA1 promoter activity and sustained elevation of serum amyloid A levels that segregated in an autosomal dominant pattern in 12 genetically affected and in none of six genetically unaffected relatives, yielding a statistically significant logarithm of odds (LOD) score over 5. Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed specifically of the SAA1.1 isoform. Tocilizumab (a monoclonal antibody against the interleukin-6 receptor) had a beneficial effect when prescribed early in the disease course. Idiopathic forms represent a significant and increasing proportion (15-20%) of all diagnosed cases of amyloid A amyloidosis. Thus, genetic screening of the SAA1 promoter should be pursued in individuals with amyloid A amyloidosis and no systemic inflammation, especially if there is a positive family history.
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Amiloidose , Amiloidose/complicações , Humanos , Mutação , Regiões Promotoras Genéticas , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/metabolismoRESUMO
Background: Factor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data. Methods: A total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR). Results: Eight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters. Conclusions: Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.
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Complexo Antígeno-Anticorpo/imunologia , Biomarcadores , Complemento C3/imunologia , Proteínas do Sistema Complemento/genética , Proteínas do Sistema Complemento/metabolismo , Variação Genética , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/etiologia , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Ativação do Complemento , Gerenciamento Clínico , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Predisposição Genética para Doença , Glomerulonefrite Membranoproliferativa/diagnóstico , Glomerulonefrite Membranoproliferativa/mortalidade , Humanos , Testes de Função Renal , Masculino , Polimorfismo de Nucleotídeo Único , Prognóstico , Curva ROC , Avaliação de Sintomas , Adulto JovemRESUMO
Renal failure is a serious complication of multiple myeloma, and up to 50% of patients with this most frequent haematological malignancy may develop some form of renal impairment. The aetiology of renal damage is multifactorial, but increased production of free light chains that are filtered into the urine is crucial for the development of renal failure and could be associated with distal tubule involvement (myeloma kidney, light chain cast nephropathy) or with fully developed Fanconi syndrome in proximal tubule damage (proximal tubulopathy, light chain proximal tubulopathy). Glomerular damage most often manifests as AL amyloidosis or light chain deposition disease; both cause severe nephrotic syndrome. Early and adequate chemotherapy in association with symptomatic treatment can lead to rapid reduction of serum light chain concentration which is necessary to prevent development of renal failure. At present, effective therapeutic procedures can be used for this purpose, where especially a triple combination of treatment containing one of the proteasome inhibitors (bortezomib, carfilzomib or ixazomib) is able to elicit a haematological response within a few days. If there is a good haematological response to treatment, up to 50% of patients with renal failure will restore their renal function. Renal function repair can be accelerated by removing light chains from serum by dialysis with high-cutoff membrane (HCO-HD). Using this procedure can increase the chance of dialysis independence in more than 60% of patients with renal failure. Data from previously published studies on HCO-HD (MYRE or EuLITE study) have not yielded as optimistic results as originally expected, however, HCO-HD could be beneficial for some subgroup of patients with renal failure in myeloma kidney. Despite the fact that overall prognosis and survival of patients with multiple myeloma have dramatically improved, the condition with renal failure in these patients remains serious.
Assuntos
Nefropatias , Mieloma Múltiplo , Insuficiência Renal , Bortezomib , Humanos , Cadeias Leves de Imunoglobulina , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Diálise Renal , Insuficiência Renal/etiologia , Insuficiência Renal/terapiaRESUMO
BACKGROUND: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers. METHODS: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated. RESULTS: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2. CONCLUSIONS: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.
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AL amyloidosis (light chain; previously also called primary amyloidosis) is a systemic disease characterized by an amyloid deposition process affecting many organs, and which still has unsatisfactory survival of patients. The monoclonal light chains kappa (κ) or lambda (λ) or their fragments form the fibrils that deposit and accumulate in different tissues. Renal involvement is very frequent in AL amyloidosis and can lead to the development of nephrotic syndrome followed by renal failure in some cases. AL amyloidosis ultimately leads to destruction of tissues and progressive disease. With recent advances in the treatment, the importance of an early diagnosis of amyloidosis and correct assessment of its type is high. Histologic confirmation is based on Congo red detection of amyloid deposits in tissues but AL amyloidosis must also be distinguished from other systemic forms of amyloidoses with renal involvement, such as AA amyloidosis, amyloidosis with heavy chain deposition, fibrinogen Aα or ALECT2 (leukocyte chemotactic factor 2) deposition. Immunofluorescence (IF) plays a key role here. IF on formalin-fixed paraffin-embedded tissue after protease digestion, immunohistochemistry or laser microdissection with mass spectrometry should complete the diagnosis in unclear cases. Standard treatment with melphalan and prednisolone or with cyclophosphamide and dexamethasone has been replaced with newer drugs used for the treatment of multiple myeloma-bortezomib, carfilzomib and ixazomib or thalidomide, lenalidomide and pomalidomide. High-dose melphalan supported by autologous stem cell transplantation remains the therapeutic option for patients with low-risk status. These new treatment options prolong survival from months to years and improve the prognosis in a majority of patients.
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Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Terapia Combinada , Humanos , PrognósticoRESUMO
OBJECTIVES: Information on renal function required before specified radiological examinations with contrast agents is usually obtained through prediction equations using serum creatinine and anthropometric data. The aim of our study was to demonstrate discrepancy between poor prediction and good diagnostic accuracy of glomerular filtration rate (GFR) estimated by prediction equations. METHODS: In 50 patients, reference GFR was measured as plasma clearance of 51-chromium labeled ethylene-diamine-tetraacetic-acid (51Cr-EDTA) and compared with GFR assayed by creatinine clearance (CC) and estimated by Cockcroft-Gault prediction equation (CG). For comparisons, CC and CG were considered as continuous, categorical, and binary variables. Accuracy of the reference GFR prediction was expressed in terms of prediction errors and diagnostic accuracy indices. RESULTS: As continuous variable, CG estimated individual values of GFR with large prediction error exceeding that of CC. As categorical variable, it classified the patient stage of chronic kidney disease (CKD) with medium diagnostic accuracy of 74% (CKD 3) and 62% (CKD 4). As binary variable, CG classified individual patient's GFR below 30 and 60 ml/min/1.73 m2 with good diagnostic accuracy of 80 and 94%, respectively. Performance of other prediction equations did not significantly differ from CG. CONCLUSIONS: Despite large variance and poor prediction accuracy of individual GFR estimates, most of them correctly classified individual patient's GFR below specified level. Results of prediction equations thus should be used and reported exclusively as binary variables, while numerical values of GFR, if required, should be measured by more accurate radionuclide or laboratory methods. KEY POINTS: ⢠Radiological guidelines on contrast media require estimation of glomerular filtration rate to assess kidney function before specified contrast examinations. ⢠Estimated glomerular filtration rate is obtained through prediction equations using serum creatinine and anthropometric data as predictors. ⢠While numerical estimates of glomerular filtration rate are inaccurate (their prediction accuracy is poor), diagnostic accuracy of binary estimates (ability to classify patient's glomerular filtration rate below or above a specified level) is very good.
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Meios de Contraste/administração & dosagem , Creatinina/sangue , Taxa de Filtração Glomerular/fisiologia , Rim/diagnóstico por imagem , Radiografia/métodos , Insuficiência Renal Crônica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intravenosas , Rim/metabolismo , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: The non-invasive assessment of amyloid heart disease may be challenging. Cardiac magnetic resonance (CMR) represents a method of choice for assessment of left ventricular (LV) morphology and function, and it also provides a unique possibility to evaluate the presence of amyloid deposition by the late gadolinium enhancement (LGE) technique. However, so far, published studies have not been consistent in terms of described LGE patterns associated with amyloid cardiomyopathy. AIMS: To compare echocardiographic and CMR assessment of LV morphology and function and to evaluate the presence and pattern of LGE in a population of patients with AL amyloid cardiomyopathy. METHODS: Twenty-two consecutive patients with newly diagnosed AL amyloid cardiomyopathy and without contraindications to CMR were comprehensively examined by echocardiography and CMR. RESULTS: Echocardiography and CMR did not differ in the evaluation of interventricular septal thickness, LV end-diastolic diameter and ejection fraction. Significant differences were found between echocardiographic and CMR estimates of LV end-diastolic volume (P<0·01) and LV mass (P<0·001). Various global LGE patterns (transmural homogenous or heterogeneous, subendocardial) were present in 17 patients (77%), patchy LGE was observed in one case (4·5%) and suboptimal nulling of the myocardium was reported in two subjects (9%). CONCLUSIONS: Echocardiography significantly overestimates LV mass and underestimates LV volumes in patients with AL amyloid cardiomyopathy as compared to CMR. As it is present in more than three quarters of individuals with AL amyloid cardiomyopathy, any type of global LGE pattern may be considered as pathogenomic for amyloid heart disease.
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Amiloidose/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Ecocardiografia , Imagem Cinética por Ressonância Magnética/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Amiloidose/complicações , Cardiomiopatias/complicações , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Disfunção Ventricular Esquerda/etiologiaRESUMO
Multiple myeloma associated with an increased FLC production causes renal failure (cast nephropathy) requiring dialysis. Theralite is a dialyser with a high cut-off membrane (HCO) - with large size pores that allow permeability for substances of molecular masses up to 45 kDa. The FLC concentrations over hemodialysis will significantly decrease and if hematological treatment is also effective, the FLC production will significantly fall as well. The aim of this comprehensive therapy is to improve the renal functions to such an extent that a substantial removal of FLC (70-90 %) is reached in patients and even interruption of dialysis therapy (50-75 %). The number of HD with this membrane rather varies in individual patients according to the literature (e.g. an average of 12 HDs/per 1 patient - 3-45). Our cohort comprised 17 patients aged 38-71 years, with 9 HDs per 1 patient, 10 patients (59 %) stopped the dialysis therapy and 7 remained on the dialysis programme. FLC removal reached 87 % in the whole cohort after the completed HDs with Theralite, but it specifically reached 93 % in the patients without further dialysis therapy, as opposed to 75 % in those who continued to undergo HD. No patient died when receiving HD with Theralite, in 4 complications occurred without causing interruption of the therapy. We assume that monitoring FLC concentrations before each dialysis may be of prognostic significance for patients including the length of treatment with an HCO membrane. Close cooperation with a hematologist is necessary.Key words: cast nephropathy - FLC - HCO membrane - multiple myeloma - kidney failure - Theralite.
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Injúria Renal Aguda , Soluções para Diálise , Mieloma Múltiplo/complicações , Diálise Renal , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Adulto , Idoso , Feminino , Humanos , Cadeias Leves de Imunoglobulina , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
The Gitelman syndrome (GS) is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis and presence of hypocalciuria and hypomagnesemia. It is one of the most common congenital "salt-wasting" tubulo-pathies, where the impairment of function of the Na+-Cl- cotransporter (NCCT) in the distal convoluted tubule is primary and hypokalemia secondary. Hypomagnesemia is caused by the impairment of magnesium reabsorption through TRPM6 channel which is located just by NCCT. Clinically, patients suffer from fatigue and hypotension due to loss of salt and water and also have cramps and tetany. In some patients chondrocalcinosis can be identified which leads to protracted pain and repeated aseptic inflammations in the joints. The course of the disease, though, is typically benign, and it rarely leads to structural changes in the kidneys or renal impairment. In the period of 2004-2006 we commenced examination of patients with suspected GS based on clinical and laboratory findings within a grant project in the Czech Republic, and in the following years this methodology was introduced to the common laboratory practice. By the year 2011 we had identified 7 different causal mutations in the gene SLC12A3 (4 of them new) among the Czech population, which is responsible for the origin of this disease. The majority of patients, whose clinical findings indicated the presence of GS, had the mutation actually detected, specifically in heterozygous form; 4 individuals were then homozygous. Most of the identified mutations were missense mutations and the most common type found among the Czech population was the change 1315 G>A within the geneSLC12A3, which causes impairment of glycosylation of the NCCT transporter. Further a great number of single-nucleotide polymorphisms were found that may be involved in clinical manifestation of the disease.Key words: gene mutation - gene sequence - Gitelman´s syndrome - NCC channel - PCR.
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Síndrome de Gitelman/complicações , Hipopotassemia/etiologia , Membro 3 da Família 12 de Carreador de Soluto , República Tcheca , Análise Mutacional de DNA , Síndrome de Gitelman/genética , Humanos , Rim , Mutação , Receptores de Droga , Membro 3 da Família 12 de Carreador de Soluto/genética , Membro 3 da Família 12 de Carreador de Soluto/fisiologiaRESUMO
BACKGROUND: Autoantibodies against monomeric C-reactive protein (anti-CRP-Ab) observed in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) were suggested to be associated with active LN and a poor response to therapy during short-term follow-up. The aim of this study was to confirm this finding and to investigate the prognostic value of anti-CRP-Ab in patients with LN during long-term follow-up. METHODS: Sera of 57 SLE patients (47 women, 10 men) with biopsy proven LN and 122 healthy individuals were analyzed for the presence of anti-CRP-Ab by in-house ELISA. Anti-CRP-Ab levels were studied in relation to routine laboratory tests, urine analysis, levels of C3, C4, other immunological markers and the overall disease activity as assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The prognostic value of anti-CRP-Ab was tested in a subgroup of 29 newly diagnosed LN patients (median follow-up 5.9 years). Response to therapy at various time points was assessed with respect to baseline anti-CRP-Ab levels. At least partial response in the first/second year of treatment was considered as a "favorable outcome", while non-response, renal flare or end stage renal disease were considered as "unfavorable outcome". RESULTS: Anti-CRP-Ab were only detected in patients with active renal disease and their levels correlated with SLEDAI (rs = 0.165, p = 0.002). The time to response was shorter in patients being anti-CRP-Ab negative at baseline compared to anti-CRP-Ab positive patients, p = 0.037. In the second year of therapy, baseline anti-CRP-Ab positivity was a significant predictor of "unfavorable outcome" (OR [95% CI] = 15.6 [1.2-771]; p = 0.021). The predictive value of "baseline anti-CRP positivity" further increased when combined with "non-response to therapy in the first year". Baseline anti-CRP-Ab positivity was not a predictor of "unfavorable outcome" at the end of follow-up, (OR [95% CI] = 5.5 [0.6-71.1], p = 0.169). CONCLUSIONS: Baseline serum levels of anti-CRP-Ab seem to be a strong risk factor for a composite outcome of non-response, renal flare or end stage renal disease after two years of standard treatment of LN. The response to therapy seems to be delayed in anti-CRP-Ab positive patients.
Assuntos
Autoanticorpos/sangue , Biomarcadores/sangue , Proteína C-Reativa/imunologia , Nefrite Lúpica/imunologia , Adulto , Autoanticorpos/imunologia , Autoantígenos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Nefrite Lúpica/sangue , Masculino , Prognóstico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: We describe data on 10,472 renal biopsies gathered by the Czech Registry of Renal Biopsies over a period of 18 years. METHODS: We assessed the main demographic, clinical and histological data of individuals who underwent renal biopsies of native kidneys in 31 centers in the Czech Republic (population 10.3 million) during the period 1994-2011. RESULTS: We evaluated 10,472 renal biopsies: males 57.8%, children (≤15 years) 13.6%, elderly (>60 years) 19.1%. The most frequent biopsy-proven diseases were primary (55.7%) and secondary (29.1%) glomerulonephritides (GN). Tubulointerstitial nephritis (TIN) was observed in 3.4 % and vascular diseases in 4.1%. The samples were non-diagnostic in 4.2%. Among primary GN the most frequent diagnoses were IgA nephropathy (IgAN) (37.4%), membranous GN (MGN) (13%) and focal segmental glomerulosclerosis (FSGS) (12.6%). Among secondary GN, systemic lupus erythematosus (SLE) represented 23.2%, hereditary diseases 19.8% and necrotizing vasculitis (NV) 19.4%. Among adults, mild renal insufficiency [serum creatinine (SCr) 111-200 µmol/l] was present in 24.7%, advanced renal insufficiency (SCr 201-400 µmol/l) in 15.3, and 12.3% of patients had SCr > 400 µmol/l. The most common diseases in patients with nephrotic proteinuria were minimal change disease (MCD) (39.7%) among children, IgAN (26.2%) in adults aged 16-60 years and amyloidosis (42.7%) among the elderly. The mean annual incidence (per million population) was: primary GN 30.9, secondary GN 18.1, IgAN 11.6, MGN 4.0, SLE 4.0, FSGS 3.9, MCD 3.4, NV 3.2, diabetic nephropathy 2.3, thin basement membrane glomerulopathy 2.0, mesangioproliferative GN 1.9, and TIN 1.9. Ultrasound needle guidance was used in 66.8%. The frequency of serious complications (symptomatic hematoma, gross hematuria, blood transfusion) was approximately 3.2%. CONCLUSIONS: This report provides representative population-based data on native biopsy-proven renal diseases in the Czech Republic. Over the 18 years of nationwide biopsy survey, we noted an increase of the mean age of renal biopsy cases, an increasing proportion of elderly, and a cardinal change in biopsy technique towards ultrasonography needle guidance.
Assuntos
Nefropatias/epidemiologia , Nefropatias/patologia , Rim/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/patologia , Criança , Pré-Escolar , República Tcheca/epidemiologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/patologia , Feminino , Glomerulonefrite/epidemiologia , Glomerulonefrite/patologia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Necrose/epidemiologia , Necrose/etiologia , Necrose/patologia , Nefrite Hereditária/patologia , Nefrose Lipoide/epidemiologia , Nefrose Lipoide/patologia , Sistema de Registros , Insuficiência Renal Crônica/patologia , Vasculite/complicações , Vasculite/epidemiologia , Vasculite/patologia , Adulto JovemRESUMO
The amyloidoses represent a group of diseases characterized by extracellular deposition of abnormal protein, amyloid, which is formed by insoluble extracellular fibrils in ß-pleated sheets. Although cardiac involvement may occur in all types of amyloidoses, clinically relevant amyloid cardiomyopathy is a typical feature of AL amyloidosis and transthyretin-related amyloidoses. Congestive heart failure represents the commonest manifestation of amyloid heart disease. Noninvasive imaging techniques, especially echocardiography and cardiac magnetic resonance, play a major role in the diagnosis of amyloid cardiomyopathy; however, histological confirmation and exact typing of amyloid deposits is necessary whether in extracardiac location or directly in the myocardium. Early diagnosis of amyloid heart disease is of utmost importance as the presence and especially the severity of cardiac involvement generally drives the prognosis of affected subjects and plays a major role in determining the intensity of specific treatment, namely in AL amyloidosis. The management of patients with amyloid heart disease is complex. Loop diuretics together with aldosterone antagonists represent the basis for influencing signs of congestion. In AL amyloidosis, high-dose chemotherapy followed by autologous stem cell transplantation is generally considered to be a front-line treatment option, if the disease is diagnosed at its early stage. The combination of mephalan with dexamethasone has been the standard therapy for severely affected individuals; however, the combinations with several novel agents including immunomodulatory drugs and bortezomibe have been tested in clinical trials with promising results. New therapeutic substances with the potential to slow or even stop the progression of transthyretin-related amyloidosis are also extensively studied.