Septic acute kidney injury and gut microbiome: Should we change our approach?

Incidence of acute kidney injury (AKI) remained relatively stable over the last decade and the adjusted risks for it and mortality are similar across different continents and regions. Also, the mortality of septic-AKI can reach 70% in critically-ill patients. These sole facts can give rise to a question: is there something we do not understand yet? Currently, there are no specific therapies for septic AKI and the treatment aims only to maintain the mean arterial pressure over 65mmHg by ensuring a good fluid resuscitation and by using vasopressors, along with antibiotics. On the other hand, there is an increased concern about the different hemodynamic changes in septic AKI versus other forms and the link between the gut microbiome and the severity of septic AKI. Fortunately, progress has been made in the form of administration of pre- and probiotics, short chain fatty acids (SCFA), especially acetate, and also broad-spectrum antibiotics or selective decontaminants of the digestive tract in a successful attempt to modulate the microbial flora and to decrease both the severity of AKI and mortality. In conclusion, septic-AKI is a severe form of kidney injury, with particular hemodynamic changes and with a strong link between the kidney and the gut microbiome. By modulating the immune response we could not only treat but also prevent severe forms. The most difficult part is to categorize patients and to better understand the key mechanisms of inflammation and cellular adaptation to the injury, as these mechanisms can serve in the future as target therapies.

Septic acute kidney injury and gut microbiome: Should we change our approach? / Lesión renal aguda secundaria a sepsis y microbioma intestinal: ¿debemos modificar nuestro enfoque?

Incidence of acute kidney injury (AKI) remained relatively stable over the last decade and the adjusted risks for it and mortality are similar across different continents and regions. Also, the mortality of septic-AKI can reach 70% in critically-ill patients. These sole facts can give rise to a question: is there something we do not understand yet? Currently, there are no specific therapies for septic AKI and the treatment aims only to maintain the mean arterial pressure over 65mmHg by ensuring a good fluid resuscitation and by using vasopressors, along with antibiotics. On the other hand, there is an increased concern about the different hemodynamic changes in septic AKI versus other forms and the link between the gut microbiome and the severity of septic AKI. Fortunately, progress has been made in the form of administration of pre- and probiotics, short chain fatty acids (SCFA), especially acetate, and also broad-spectrum antibiotics or selective decontaminants of the digestive tract in a successful attempt to modulate the microbial flora and to decrease both the severity of AKI and mortality. In conclusion, septic-AKI is a severe form of kidney injury, with particular hemodynamic changes and with a strong link between the kidney and the gut microbiome. By modulating the immune response we could not only treat but also prevent severe forms. The most difficult part is to categorize patients and to better understand the key mechanisms of inflammation and cellular adaptation to the injury, as these mechanisms can serve in the future as target therapies.(AU)

La incidencia de la lesión renal aguda (LRA) se ha mantenido relativamente estable a lo largo de la última década, con unos riesgos ajustados de padecer y morir a consecuencia de esta enfermedad similares en los distintos continentes y regiones. La mortalidad asociada a la LRA secundaria a sepsis puede llegar a 70% en los pacientes que se encuentran en estado crítico. Estos hechos, por sí mismos, deben llevarnos a plantearnos la siguiente pregunta: ¿se nos escapa algo que aún no comprendemos? Actualmente no se dispone de terapias específicas para la LRA secundaria a sepsis y el tratamiento se centra únicamente en mantener la presión arterial media por encima de los 65mmHg mediante una rehidratación adecuada, vasopresores y antibióticos. Asimismo, cada vez existe mayor interés por las diferentes alteraciones hemodinámicas que se producen en comparación con otras formas de la enfermedad, así como por la relación existente entre el microbioma intestinal y la gravedad. Afortunadamente, se ha avanzado notablemente en la forma en la que se administran los prebióticos y los probióticos, los ácidos grasos de cadena corta (AGCC), especialmente el acetato, los antibióticos de amplio espectro o los detoxificantes selectivos del tracto digestivo, en un intento exitoso de modular la flora microbiana y disminuir tanto la gravedad de la LRA como su mortalidad. En conclusión, la LRA secundaria a sepsis es una forma grave de lesión renal que provoca unos cambios hemodinámicos específicos y en la que se observa una estrecha relación entre la función renal y el microbioma intestinal. La modulación de la respuesta inmunitaria no solo permitiría tratar esta enfermedad, sino también prevenir las formas graves de la misma. La parte más difícil de este enfoque radica en clasificar correctamente a los pacientes y comprender mejor los mecanismos clave de la inflamación y la adaptación celular a la lesión, ya que estos pueden convertirse en futuras dianas terapéuticas.(AU)

The Role of the L-Arginine-Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease.

Recently, arginine has been proven to play an important role in ADPKD physiopathology. Arginine auxotrophy in ADPKD induces cell hyperproliferation, blocking the normal differentiation of renal tube cells and causing cyst formation. We explored the L-arginine (Arg)-nitric oxide (NO) molecular pathway in ADPKD, a multisystemic arginine auxotrophe disease. We developed a prospective case-control study that included a group of 62 ADPKD subjects with an estimated filtration rate over 60 mL/min/1.73 mp, 26 subjects with chronic kidney disease with an eGFR > 60 mL/min/1.73 mp, and a group of 37 healthy subjects. The laboratory determinations were the serum level of arginine, the enzymatic activity of arginase 2 and inducible nitric oxide synthase, the serum levels of the stable metabolites of nitric oxide (nitrate, direct nitrite, and total nitrite), and the endogenous inhibitors of nitric oxide synthesis (asymmetric dimethylarginine and symmetric dimethylarginine). In the ADPKD group, the levels of the arginine and nitric oxide metabolites were low, while the levels of the metabolization enzymes were higher compared to the control group. Statistical analysis of the correlations showed a positive association between the serum levels of Arg and the eGFR and a negative association between Arg and albuminuria. ADPKD is a metabolic kidney disease that is auxotrophic for arginine. Exploring arginine reprogramming and L-Arg-NO pathways could be an important element in the understanding of the pathogenesis and progression of ADPKD.

Disturbances in Nitric Oxide Cycle and Related Molecular Pathways in Clear Cell Renal Cell Carcinoma.

It is important to note that maintaining adequate levels of nitric oxide (NO), the turnover, and the oxidation level of nitrogen are essential for the optimal progression of cellular processes, and alterations in the NO cycle indicate a crucial step in the onset and progression of multiple diseases. Cellular accumulation of NO and reactive nitrogen species in many types of tumour cells is expressed by an increased susceptibility to oxidative stress in the tumour microenvironment. Clear cell renal cell carcinoma (ccRCC) is a progressive metabolic disease in which tumour cells can adapt to metabolic reprogramming to enhance NO production in the tumour space. Understanding the factors governing NO biosynthesis metabolites in ccRCC represents a relevant, valuable approach to studying NO-based anticancer therapy. Exploring the molecular processes mediated by NO, related disturbances in molecular pathways, and NO-mediated signalling pathways in ccRCC could have significant therapeutic implications in managing and treating this condition.

The Impact of Infections on the Progression of Chronic Kidney Disease.

Background and Objective: Infectious diseases continue to be a global burden and their impact is even worse if the patients already have other comorbidities. Because chronic kidney disease is very frequent, affecting 10% of the population, our study aims to explore the impact that infectious events have on its progression. Material and Methods: This is a retrospective, observational study based on a cohort of 238 dialyzed patients from the Nephrology Clinic of "Dr. Carol Davila" Clinical Hospital of Nephrology, Bucharest, who were followed from their first visit for five years, between 1 January 2007 and 1 January 2022. For each of them, the presence of an infectious event and the moment of the initiation of dialysis were recorded. Results: Statistical analysis showed that the patients who had at least one infectious episode were older (p = 0.004), their hemoglobin and lymphocytes were significantly lower (p = 0.03 and p = 0.02, respectively) and the time until the initiation of dialysis was lower (p = 0.007). Also, the preservation of kidney function was influenced by the number and the severity of infectious episodes. In the univariate Cox model, the following variables were associated with increased risk of dialysis: advanced age (p: 0.009; HR: 1.021; CI: 1.005 to 1.036), low hemoglobin (p: 0.001; HR: 0.861; CI: 0.786 to 0.943), previous diagnosis of chronic obstructive pulmonary disease (p: 0.002; HR: 2.467; CI: 1.376 to 4.424), presence of hematuria (p: 0.03; HR: 1.604; CI: 1.047 to 2.457) and increased values of proteinuria (p: 0.01; HR: 1.122; CI: 1.028 to 1.224) and of serum creatinine measured both at the time of the first visit and at the time of each infectious event (p: <0.001; HR: 1.262; CI: 1.141 to 1.396). Also, the presence of an infectious episode was associated with a 1.7-fold increase in the risk of dialysis initiation. The independent predictors of survival identified by the multivariate Cox model were age (p: 0.004; HR: 1.034; CI: 1.010-1.058), serum creatinine (p: <0.001; HR: 1.421; CI: 1.203 to 1.658) and proteinuria (p: <0.001; HR: 1.241; CI: 1.126 to 1.369) at the time of enrollment, but also the presence of an infectious episode during the patient's evolution (p: 0.04; HR: 1.705; CI: 1.013 to 2.868). Conclusions: In the evolution of patients with chronic kidney disease, an active search for individual factors favoring the occurrence of infectious episodes should be taken into consideration to prevent a faster progression toward end-stage kidney disease.

Chronic Kidney Disease, Urinary Tract Infections and Antibiotic Nephrotoxicity: Are There Any Relationships?

Chronic kidney disease (CKD) has been a constant burden worldwide, with a prevalence of more than 10% of the population and with mortality reaching 1.2 million deaths and 35.8 million disability-adjusted life years (DALYs) in 2017, as it is claimed by the Global Burden of Diseases. Moreover, an increase in its prevalence is expected in the next years due to a rise in the number of people suffering from obesity, diabetes mellitus and hypertension. On the other hand, with cardiovascular morbidity and mortality showing a downward trend, maybe it is time to focus on CKD, to minimize the preventable risk factors involved in its progression toward end-stage kidney disease (ESKD) and to offer a better quality of life. Another major health burden is represented by infectious diseases, particularly urinary tract infections (UTIs), as it is considered that approximately 40-50% of women and 5% of men will have at least one episode during their lifetime. Additionally, CKD consists of a constellation of immunological and metabolical disturbances that lead to a greater risk of UTIs: increased apoptosis of lymphocytes, elevated levels of tumor necrosis factor α and interleukin 6, which lower the function of neutrophils and increased levels of uremic toxins like p-cresyl sulfate and indoxyl sulfate, which alter the adherence and migration of leukocytes to the sites of injury. Moreover, UTIs can lead to a more rapid decline of kidney function, especially in stages G3-G5 of CKD, with all the complications involved. Last, but not least, antibiotherapy is often complicated in this category of patients, as antibiotics can also negatively affect the kidneys. This review will try to focus on the particularities of the urinary microbiome, asymptomatic bacteriuria and UTIs and the subtle balance between the risks of them and the risks of antibiotherapy in the evolution of CKD.

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis.

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

Sialoglyco-Conjugate Abnormalities, IL-6 Trans-Signaling and Anti-Ganglioside Immune Response-Potential Interferences in Lupus Nephritis Pathogenesis.

We have investigated glycoconjugates sialization profile, endogen synthesis rate of antiganglioside antibodies (AGA), IL-6 signaling pathways correlated with activity disease in systemic lupus erythematous (SLE) and lupus nephritis (LN). MATERIAL AND METHODS: A case-control study was developed and included 109 patients with SLE with or without renal impairment, 32 patients with IgA nephropathy and 60 healthy volunteers, clinically and paraclinically monitored. The following parameters were evaluated in volunteers serum: total sialic acid (TSA), orosomucoids, lipid bound sialic acid (LSA), interleukin-6 (IL-6), soluble factors IL-6R, gp130, anti -GM1, -GM2, -GM3, -GD1a, -GD1b, -GT1b, -GQ1b antigangliosides antibodies of IgG and IgM type. RESULTS: Experimental data analysis showed: increase in synthesis rhythm of sialoglyco-conjugated in SLE (TSA increased in SLE and LN compared to control), accelerated catabolism of LSA in LN (LSA/TSA ratio was higher in SLE and LN than in control group), overexpression of IL-6 mediated trans-signaling (sIL-6R/sgp 130 ratio was subunit in SLE and IgA nephropathy and superunit in LN), large AGA profile synthesis of IgM isotype (over 45.1% in SLE and over 20.7% in LN). CONCLUSIONS: Hypersialization, accelerated glycosphingolipids degradation, IL-6 trans-signaling amplify and AGA pattern could represent essential mechanisms in LN pathogenesis.

Pharmacokinetics, Dialysability, and Safety of Gadopiclenol, a New Gadolinium-Based Contrast Agent, in Patients With Impaired Renal Function.

OBJECTIVES: The aims of this study were to evaluate the pharmacokinetics (PK) of gadopiclenol, a new macrocyclic gadolinium based-contrast agent, in subjects with impaired renal function, and to assess its dialysability in subjects with end-stage renal disease (ESRD). METHODS AND MATERIALS: This 2-center, open-label, phase 1 study included 5 successive cohorts of 8 adult subjects: healthy subjects (cohort 1), subjects with mild (cohort 2), moderate (cohort 3), severe (cohort 4) renal impairment, or ESRD (cohort 5), who received a single intravenous injection of gadopiclenol (0.1 mmol/kg). Blood and urine samples were collected at different time points in cohorts 1 to 4, and blood and dialysate samples were collected at each hemodialysis session (4-hour session on day 1, day 3, and day 5) in cohort 5. Gadopiclenol elimination and safety were assessed for up to 6 months. Pharmacokinetics parameters were calculated using noncompartmental analysis. RESULTS: A total of 40 subjects were included, with a mean age of 51.5 years (range, 18-71 years). No significant difference in the mean maximum concentration values and the distribution volume was observed among cohorts 1 to 4. Urinary excretion of unchanged gadopiclenol was delayed with the degree of renal impairment and ranged between 96% and 84% in subjects with mild to severe renal impairment. Compared with that of healthy subjects, the mean area under the plasma concentration curve was 54%, 148%, and 769% higher in subjects with mild, moderate, or severe renal impairment, respectively. The mean terminal half-life was prolonged with the degree of renal impairment (1.9, 3.3, 3.8, and 11.7 hours for cohorts 1-4). In ESRD subjects, gadopiclenol was effectively removed from the plasma (95% to 98%) after the first hemodialysis session. Gadopiclenol concentration in plasma was below the limit of quantification for all subjects after the second hemodialysis session. Gadopiclenol concentration was below limit of quantification in all plasma and urine samples collected at 1, 3, and 6 months. Five subjects (12.5%) experienced adverse events related to gadopiclenol, none serious and all resolved. Laboratory measurements, vital signs, and electrocardiography did not raise any safety concern. CONCLUSIONS: Gadopiclenol elimination half-life was prolonged in subjects with mild to severe renal impairment, yet its renal clearance remains complete or nearly complete. In ESRD subjects, gadopiclenol was effectively removed from the plasma after 1 hemodialysis session, and up to 3 hemodialysis sessions were sufficient to completely clear it. No safety concern was raised. Therefore, no dose adjustment seems necessary in this patient population.

Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma.

Posttranslational modifications are dynamic enzymatic-mediated processes, regulated in time and space, associated with cancer development. We aimed to evaluate the significance of posttranslational modifications in the pathogenesis of clear cell renal cell carcinoma. The authors developed a prospective, observational study during a period of three years and included 55 patients with localized renal cell carcinoma and 30 heathy subjects. Glycosylation, nitration and carbonylation, thiol-disulfide homeostasis, methylation, phosphorylation and proteolytic cleavage were evaluated in the serum of the evaluated subjects in the present study. Our results showed some characteristics for early ccRCC: high production of cytokines, substrate hypersialylation, induced nitrosative and carbonylic stress, arginine hypermethylation, thiol/disulfide homeostasis (TDH) alteration, the regulatory role of soluble receptors (sRAGE, sIL-6R) in RAGE and IL-6 signaling, the modulatory effect of TK-1and TuM2-PK in controlling the level of phosphometabolites in neoplastic cells. These data could be the initial point for development of a panel of biomarkers such as total sialic acid, orosomucoids, nitrotyrosine, carbonylic metabolites, ADMA, SDMA, and thiol-disulfide equilibrium for early diagnosis of ccRCC. Moreover, they could be considered a specific disease PTM signature which underlines the transition from early to advanced stages in this neoplasia, and of a therapeutic target in kidney oncogenesis.

Clinical and pathological considerations on renal diseases in patients with chronic viral hepatitis.

Chronic viral hepatitis B and C may associate different extrahepatic manifestations and renal disease is the most frequent. Kidney damage is represented in most cases by glomerulopathies, which include membranous nephropathy, membranoproliferative glomerulonephritis (MPGN), IgA nephropathy, focal and segmental glomerulosclerosis and diabetic nephropathy. We conducted a retrospective study on 639 patients diagnosed with chronic viral hepatitis B and C and different renal diseases. Complete evaluation of liver and renal status was performed and, in selected cases, renal biopsy. The evaluation of our cases allowed us to uncover that 82 (12.8%) patients presented a renal disease that could be linked to the viral infection. In order to identify the histopathological type of the renal lesions, kidney biopsy was performed in 39 of our patients. In hepatitis B virus (HBV) infection, the most frequent glomerulopathy was represented by membranous nephropathy, while in chronic hepatitis C infection, MPGN was responsible for the majority of glomerulonephritis. Most patients with MPGN and hepatitis C virus (HCV) also presented mixed cryoglobulinemia. Immunoglobulin A (IgA) nephropathy was present in both liver diseases while diabetic nephropathy was only found in HCV infection, in the context in which chronic hepatitis C is a risk factor for the development of type II diabetes mellitus.

Monitoring Diabetic Nephropathy by Circulating Gangliosides.

Gangliosides are multifunctional molecules, abundantly expressed in renal cell membrane but also in sera of patients with renal disease. The aim of this study was to quantify the serum levels of sialic acid-ganglioside in patients diagnosed with diabetes for an eventual biomarker stratification of patients with renal complications. We included 35 diabetic patients without metabolic complications, 35 patients with diabetic nephropathy, 35 non-diabetic individuals. We found that sialic acid ganglioside serum level was significantly increased in patients with diabetic nephropathy compared to the level obtained in patients with uncomplicated diabetes and to non-diabetic controls. A statistically significant positive correlation was obtained between serum levels of sialic acid gangliosides, HbA1c, and serum creatinine in patients with diabetes without complications. Moreover positive correlation was found between sialic acid ganglioside and blood glucose, HbA1c, urea, creatinine, microalbuminuria in patients with diabetic nephropathy. We can conclude that serum sialic acid-gangliosides are statistically increased in diabetic nephropathy positively correlated with microalbuminuria.

Prevalence of chronic kidney disease and its association with cardio-metabolic risk factors in the adult Romanian population: the PREDATORR study.

PURPOSE: PREDATORR is the first national study analyzing the prevalence of chronic kidney disease and its prognosis and association with socio-demographic, cardio-metabolic and lifestyle risk factors in the adult Romanian population. METHODS: Chronic kidney disease was defined according to the KDIGO 2012 criteria as an estimated glomerular filtration rate <60 mL/min/1.73 m(2) and/or urinary albumin-to-creatinine ratio ≥30 mg/g. The socio-demographic, lifestyle and anamnestic data were collected through interviewer-administered questionnaires. Physical examination and biochemical assays were also performed. RESULTS: This cross-sectional study conducted between December 2012 and February 2014 in Romania included 2717 adults. The overall age- and sex-adjusted prevalence of chronic kidney disease was 6.74 % (95 %CI 5.60-7.88 %), of which 3.31 % (2.50-4.13 %) had only reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), 2.98 % (2.21-3.76 %) had only albuminuria, and 0.45 % (0.14-0.74 %) had both. The prevalence of chronic kidney disease increased with age and was similar in women and in men. Age, hyperuricemia, impaired glucose regulation (diabetes/prediabetes), hypertriglyceridemia and a family history of renal disease were independent risk factors for the presence of chronic kidney disease. CONCLUSIONS: The PREDATORR study showed a high prevalence of chronic kidney disease in the adult Romanian population providing data on its prognosis and association with several cardio-metabolic risk factors.

The histogenetic base of renal capsular-derived tumors.

Capsulomas comprise a category of very rare benign tumors derived from the renal capsule, the most encountered being myxomas and leiomyomas. To get more information on the histogenetic origin of these tumors, a comprehensive ultrastructural investigation on the human renal capsule has been done on kidney biopsy samples performed for nephropathologic diagnosis. The human renal capsule ultrastructure is similar to that of the mammalian renal capsule. There are two cellular layers: an inner layer made up of particular (immature) smooth muscle cells, and a second outer layer consisting of fibroblasts, collagen fibers, extracellular matrix, and telocyte-like cells. Two cases of leiomyomas of microscopic dimensions, situated beneath the capsule have been described. Data from the literature presenting the ultrastructure and perirenal location of myxomas support the affiliation of these capsulomas with the resident renal capsular cells. Based on ultrastructural studies, the authors demonstrate the presence of telocyte-like cells in the outer layer of the human renal capsule and propose distinct histogeneses for leiomyomas and for capsular myxomas as derived from the inner and outer capsular layers, respectively.

Desmosomes as markers for the proliferating parietal epithelial cells in collapsing glomerulosclerosis. A case report.

Two variants of focal segmental glomerulosclerosis are known to present epithelial hypercellularity in the Bowman's space, namely the collapsing and the cellular types. This epithelial cell proliferation may get features of either pseudocrescent or tubular profiles. Our case of collapsing focal segmental glomerulosclerosis has been ultrastructurally investigated concerning the proliferating epithelial cell type: parietal versus visceral. Based on the cellular organelles, especially on the ubiquitous presence of desmosomes, the authors are endorsing, with ultrastructural arguments, the opinion favoring the parietal epithelial cells (PEC) as the proliferating cell type. It is also taken into consideration the eventual change of PECs phenotype in contact with the glomerular tuft components like the glomerular basement membrane.

Mass spectrometry and renal calculi.

The present review represents a concise and complete survey of the literature covering 2004-2009, concerning the mass spectrometric techniques involved in the structural investigation of renal calculi. After a short presentation of the fundamental mass spectrometric techniques (MALDI-TOF, QTOF, MS-MS) as well as hyphenated methods (GC-MS, LC-MS, CE-MS), an extensive study of the urinary proteome analysis as well as the detection and quantification by mass spectrometry of toxins, drugs and metabolites from renal calculi is presented.

Tuberculin skin test, interferon-gamma assay, and T cells subpopulations in hemodialysis patients.

OBJECTIVE: To examine and compare the responses of hemodialysis (HD) patients to Mycobacterium tuberculosis antigens by using the tuberculin skin test (TST) and an interferon gamma assay (IFN-TB), and to investigate the relationship between T cells subpopulations and tests results. Observational, prospective, diagnostic study conducted in a HD center in a country with high prevalence of tuberculosis. PATIENTS: 195 patients on maintenance HD who consented to participate in this study; 187 (6 were excluded for refusing TST and 2 for indeterminate responses to IFN-TB) were HIV negative, vaccinated with the Bacille Calmette-Guerin vaccine, and without any signs of active tuberculosis, were selected. METHODS: Similar to the Mantoux method, 10 IU tuberculin was used for the TST. An IFN-gamma assay specific for Mycobacterium tuberculosis antigens and phytohemagglutinin was carried out. Flow cytometry analysis of peripheral lymphocytes was also performed. RESULTS: TST and IFN-TB results were found to be positive (44% and 53%, respectively) or negative (32% and 47%, respectively) in similar proportions. Results were in agreement in 71% of positive and 58% of negative tests. IFN-gamma levels were found to be higher in patients with a positive TST. All cell counts and CD4/CD8 were found to be higher in TST-positive patients, whereas only total lymphocytes count and CD4/CD8 were reported to be high in IFN-TB-positive patients. A model of multivariable linear regression including cell counts explained 16% of the mitogen-induced IFN-gamma production (F = 5,11; P = .0003). The majority of subjects with positive tests were younger, in most cases male, belonged to the Roma ethnic group, had a shorter HD vintage, and a better nutritional status. CONCLUSIONS: TST and IFN-gamma production stimulated by Mycobacterium tuberculosis antigens rely on patient's immune status, which could be influenced by either individual (age, gender), dialysis-related (HD vintage), or nutritional factors. In addition, the diagnostic utility for tuberculosis is similar and moderate in HD patients.

Amiloidosis, a mysterious disease, still underestimated.

Amyloidosis, 150 years after being identified, still remains a mysterious disease, full of mystery, question marks and challenges, almost always ignored from the start, with terrible symptoms and terrible prognosis. The mechanics of the formation. persistence and setting of the amyloid fibrils are still under discussion. This article wishes to point out some of the main characteristics of this disease and the involved proteins by referring to the history. The pathogenesis, the histology, the diagnosis and a few aspects of the prognosis of this disease in the hope that future research will bring to light the answers for the mystery of amyloidosis along with more efficient therapies.