The Artificial Neural Network as a Diagnostic Tool of the Risk of Clostridioides difficile Infection among Patients with Chronic Kidney Disease.

The majority of recently published studies indicate a greater incidence and mortality due to Clostridioides difficile infection (CDI) in patients with chronic kidney disease (CKD). Hospitalization, older age, the use of antibiotics, immunosuppression, proton pump inhibitors (PPI), and chronic diseases such as CKD are responsible for the increased prevalence of infections. The aim of the study is to identify clinical indicators allowing, in combination with artificial intelligence (AI) techniques, the most accurate assessment of the patients being at elevated risk of CDI.

Clinical Determinants Predicting Clostridioides difficile Infection among Patients with Chronic Kidney Disease.

The majority of recently published studies indicate a greater incidence rate and mortality due to Clostridioides difficile infection (CDI) in patients with chronic kidney disease (CKD). The aim of this study was to assess the clinical determinants predicting CDI among hospitalized patients with CKD and refine methods of prevention. We evaluated the medical records of 279 patients treated at a nephrological department with symptoms suggesting CDI, of whom 93 tested positive for CDI. The survey showed that age, poor kidney function, high Padua prediction score (PPS) and patients' classification of care at admission, treatment with antibiotics, and time of its duration were significantly higher or more frequent among patients who suffered CDI. Whereas BMI, Norton scale (ANSS) and serum albumin concentration were significantly lowered among CDI patients. In a multivariate analysis we proved the stage of CKD and length of antibiotics use increased the risk of CDI, whereas higher serum albumin concentration and ANSS have a protective impact.

Focal and segmental glomerulosclerosis in adults: early clinical course and prognostic factors for short-term outcome / Glomeruloesclerosis focal y segmentariaenadultos: evoluciónclínicatemprana y factorespronósticos de resultados a cortoplazo

ABSTRACT Background: Primary focal and segmental glomerulosclerosis progresses to end-stage renal disease in every other patient, and therefore determinants of its long-term outcome have been extensively studied. Immediate response to treatment has been regarded as a positive prognostic predictor and short-term manifestation of the disease could affect its determinants. Therefore, we have sought to assess the early clinical course of primary adult focal and segmental glomerulosclerosis and analyze its prognostic factors. Methods: We have retrospectively assessed clinical course of primary focal and segmental glomerulosclerosis ("not otherwise specified" histological variant) in 84 adults. Renal function was expressed as serum creatinine concentration and equilibrated glomerular filtration rate (MDRD equation). Proteinuria was expressed as protein to urinary creatinine ratio, assessed in the morning voiding sample. The evaluation of these parameters was performed every 3 months after diagnosis. Statistical analysis was achieved using package Statistica. Results: As result of treatment, complete remission of proteinuria, was attained in 30 subjects (35.7%), partial remission in 37 persons (44%), whereas in 17 patients protein excretion rate remained unchanged (20.2%). The severity of glomerular injury, at initial presentation of the disease, correlated with its early (12 months) outcome: patients attaining early complete remission have had the lowest initial proteinuria, higher serum albumin and total protein concentrations than those who have failed to achieve remission. Pharmacotherapy with prednisone, but not with calcineurin inhibitors or mycophenolate mofetil was demonstrated to significantly affect achievement of remission. Conclusions: Early remission of proteinuria in response to treatment is feasible in 44% of patients with primary focal and segmental glomerulosclerosis, it is best achieved in subjects presenting with mild glomerular injury, and in patients treated with prednisone. Higher serum albumin and total protein concentrations predict better response to induction of remission.

RESUMEN Antecedentes: La glomeruloesclerosis focal y segmentaria se convierteennefropatía terminal enuno de cada dos pacientes, por lo que losfactoresdeterminantes de susdesenlaces a largo plazohansidoobjeto de muchosestudios. La respuestainmediata al tratamiento se considera un factor pronóstico favorable, y las manifestaciones a cortoplazo de la enfermedadpuedenafectarlosfactoresdeterminantes. Portodoello, hemosbuscadoevaluar la evoluciónclínicatemprana de la glomeruloesclerosis focal y segmentariaprimaria, y analizarsusfactorespronósticos. Material y métodos: Hemosrealizado un estudioretrospectivo para evaluar la evoluciónclínica de la glomeruloesclerosis focal y segmentariaprimaria (variantehistológica "sin otraespecificación") en 84 pacientesadultos. Se evaluó la función renal a través de la creatininasérica y filtrado glomerular equilibradocalculadomediante la ecuación MDRD. La proteinuria se expresócomorelaciónproteína/creatininaurinaria, evaluadaen la muestramiccionalmatutina. La evaluación de estosparámetros se realizócada 3 mesesdespués del diagnóstico. El análisisestadístico se logróutilizando el paqueteStatistica. Resultados: Como resultado del tratamiento, se obtuvounaremisióncompleta de la proteinuria en 30 sujetos (35,7%), unaremisiónparcialen 37 personas (44%), mientras que, en 17 pacientes, la tasa de excreción de proteínas se mantuvo sin cambios (20,2%). En la presentacióninicial de la enfermedad, la gravedad de la lesión glomerular se correlacionó con suresultadotemprano (12 meses): lospacientes que lograronunaremisióncompletatempranamostraronlosnivelesmásbajos de proteinuria inicial, y concentracionesmásaltas de albúminasérica y proteínastotales que aquellos que no alcanzaron la remisión. Se demostró que la farmacoterapia con prednisona -pero no con inhibidores de calcineurina o micofenolato de mofetilo- condiciona de forma significativa el logro de la remisión. Conclusiones: La remisióntemprana de la proteinuria enrespuesta al tratamientoesfactibleen el 44% de lospacientes con glomeruloesclerosis focal y segmentariaprimaria; se obtienenmejoresresultadosensujetos que presentanunalesión glomerular leve y enpacientestratados con prednisona. Las concentracionesmásaltas de albúminasérica y proteínastotalespredicenunamejorrespuesta para inducir la remisión.

[i]Clostridioides difficile[/i] infection in patients with end stage renal disease. Is it preventable?

[i]Clostridioides difficile[/i] infection (CDI) is a leading cause of a healthcare-associated diarrhea worldwide. Recently, an increased number of new cases and growing mortality due to CDI have been observed. Patients suffering from end-stage renal disease (ESRD) are most exposed to CDI. It has been proven that CDI in patients receiving renal replacement therapy (RRT) significantly increases mortality, prolongs hospitalization and increases the cost of treatment. Important risk factors of CDI in ERSD patients include hospitalization or stay in an intensive care unit in the last 90 days, HIV infection, bacteremia, prolonged antibiotic therapy and hypoalbuminemia. Cirrhosis, age over 65 years, hypoalbuminemia, longer hospitalization time and use of antibiotics are significant risk factors of death. Effective methods of preventing CDI include hand hygiene with soap and water, isolation of infected patients in a private room with a dedicated toilet, the use of masks, gloves, disinfection of the environment and systematic education and control of medical personnel, as well as rational antibiotic policy. In addition, it is important to avoid antibiotics with a proven risk of CDI, caution use of proton pump inhibitors (PPI) and H2 receptor antagonists. It is also important in the prevention of CDI in people with ERSD, to apply a fast diagnostic since the onset of the first symptoms. The use of probiotics and bile acids in the primary prevention of CDI requires further research. It seems that knowledge of these factors and methods of prevention will significantly reduce morbidity and mortality due to CDI.

Glomerular podocytes in diabetic renal disease.

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD), both in the USA and in Europe; moreover, its incidence is rising worldwide. The main laboratory markers of DN progression are albuminuria and a reduction in glomerular filtration rates, although progression of the disease has been observed even in the absence of these biomarkers. Renal impairment, associated with diabetes, results from damage to the glomerular filtration barrier, at the level of highly differentiated glomerular epithelial cells: podocytes. These cells regulate glomerular filtration and many immunological processes occurring at this level. The earliest possible diagnosis of diabetic kidney disease (DKD) and implementation of intensive treatment offers the possibility of preventing or substantially delaying the onset of ESRD. In this article, we review various urinary biomarkers linked with glomerular podocyte cytophysiology as potentially sensitive diagnostic tools for the early detection of DKD. These biomarkers have predictive potential for assessing the progression toward end-stage nephropathy.

Celiac disease: uncommon, oligosymptomatic course of illness, with profound hypoalbuminemia in an adult patient.

Celiac disease (CD) is an immune-mediated disease, caused by gluten, occurring in people with genetic predisposition. The course of the disease can vary and includes both intestinal and extra-intestinal manifestations. Many patients are undiagnosed for many years and some of them, in particular with nonspecific symptoms or asymptomatic, might never be diagnosed. We present a rare case of a patient, who's first and practically the only symptom of the disease was a pathological fracture of the ribs. In addition, despite the lack of clinical symptoms of malabsorption syndrome, malnutrition and proteinuria, we observed profound hypoalbuminemia and hypoproteinemia. This case suggests that CD diagnostic should be undertaken in evaluation of every patient with osteoporotic fractures and hypoalbuminemia.

Risk factors of the Clostridium difficile infection in patients with chronic kidney disease.

BACKGROUND: Clostridium difficile (C. difficile) is a Gram-positive bacillus responsible for diarrhea and colitis, mainly among hospitalized patients. It is a leading cause of nosocomial infections. OBJECTIVES: The main goal of the study was to assess the risk factors of the C. difficile infection in patients with chronic kidney disease (CKD). MATERIAL AND METHODS: We evaluated the medical records of all patients treated at the Department of Nephrology and Renal Transplantation of the Research and Development Center in the Provincial Specialist Hospital in Wroclaw, Poland, between February 2009 and May 2012, who developed diarrhea, abdominal pain and/or fever within 72 h after admission. In patients with these symptoms, an enzyme cassette immunoassay was performed to detect antigens of C. difficile toxins A and B in stool. RESULTS: There were 207 patients enrolled in the study, presented with the symptoms of the C. difficile infection. Out of these patients, 69 (33%) persons were positive for C. difficile toxins. Longer hospitalization time and lower initial serum albumin concentration significantly increased the risk of infection (p < 0.05). Apart from the C. difficile infection, age, the number of used antibiotics, longer hospitalization time, and lower initial serum albumin concentration significantly augmented the risk of death (p < 0.05). CONCLUSIONS: In patients with CKD, longer hospitalization time and lower serum albumin concentration significantly increased the risk of the C. difficile infection. The C. difficile infection, age, the number of used antibiotics, longer hospitalization time, and lower initial serum albumin concentration notably augmented the risk of death. Although the incidence of the C. difficile infection did not correlate with the estimated glomerular filtration rate (eGFR), 67% of patients who tested positive were class 5 of CKD, whereas only 5.7% were class 1.

Clinicopathologic correlations of renal pathology in the adult population of Poland.

BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.

Breast Involvement in Anti-Neutrophil Cytoplasmic Antibodies Positive Granulomatosis With Polyangiitis in a 64-Year-Old Female Patient.

In this article, we present a case of a female patient suffering from granulomatosis and polyangiitis with active glomerular disease, who developed exacerbation of pulmonary vasculitis and palpable tumors of right breast. A possibility of neoplastic disease was excluded by histopathological examination of percutaneous biopsy specimen, revealing granulomatous inflammatory infiltrate, without any features of neoplasia. Moreover, both pulmonary and breast lesions subsided following intensification of immunosuppressive/antiinflammatory treatment.

Expression of Cell Membrane Antigens in Cells Excreted in the Urinary Sediment Predicts Progression of Renal Disease in Patients with Focal Segmental Glomerulosclerosis.

BACKGROUND/AIMS: A link between the number of podocytes excreted in the urine and activity of glomerular disease has been established. The aim of this study was to investigate possible correlations between urinary cells' phenotype and the progression of focal segmental glomerulosclerosis (FSGS). METHODS: Forty patients with newly diagnosed FSGS were included. Cells were isolated from urine by adherence to collagen-coated cover slips and assessed for the expression of podocalyxin (PDX), CD68 and Ki67 antigens by indirect immunofluorescence. In addition, double-staining procedures were performed in combinations of the above antigens plus cytokeratin, WT1 and CD-105. Twenty-two patients in whom urinary protein to creatinine ratio exceeded 2.0 at diagnosis were followed for 36 months, with assessments of renal function and proteinuria every 3 months. During observation, patients were subjected to standard therapy. RESULTS: Significantly higher numbers of Ki67 positive cells at the onset of the study were observed in patients who have doubled serum creatinine (SCr) in follow-up, than in those who have not (p = 0.0149). By logistic regression analysis, both CD68 and Ki67, but not anti-PDX positive cell numbers at diagnosis were found to be predictors of doubling SCr concentration in 36 months' follow-up. Results of double staining indicate that PDX positive cells could be identified as podocytes or their precursors and parietal epithelial cells. CONCLUSION: Urinary sediment PDX positive cell numbers do not predict the progression of FSGS, whereas CD68 and Ki67 phenotype of urinary podocytic lineage clearly has a prognostic significance in 36 months' observation of primary FSGS.

[ANCA associated vasculitis]. / Ukladowe zapalenia naczyn zwiazane z wystepowaniem przeciwcial przeciwko cytoplazmie neutrofili--ANCA.

Vasculitis is a process caused by inflammation and necrosis of blood vessel walls and results in a variety of disorders. An accepted classification system for vasculitis is categorized by the size or type of the involved blood vessel as large-, medium-, or small-vessel vasculitis. Small-vessel vasculitis is defined as vasculitis that affects vessels smaller than arteries (i.e., arterioles, venules, and capillaries); however, small-vessel vasculitis can also involve medium-sized arteries. Granulomatosis with polyangiitis, Microscopoc polyangiitis, Churg Strauss syndrome and Renal Limited Vasculitis where the kidney is the only organ involved are clasified as a small vesselvasculitis. These disorders are described to be commonly associated with antineutrophil cytoplasm antibodies (ANCA). The etiology is not known and the incidence of vasculitis is incresasing occuring more often in elderly population. These diseases can cause the focal necrotizing lesions witch affect vessels and organs. In the lung it may cause alveolar hemorrhage, in the kidneys crescentic glomerulonephritis with acute renal failure, in the skin purpuric rash and ulcerations. Treatment usually includes corticosteroids, immunosupresive therapy and in some cases plasmapheresis. Advances in clinical management have been achieved during the past few years.

[Significance of podocytes isolated from urine as a marker of glomerulonephritis activity--is the game worth of a candle?]. / Znaczenie podocytów izolowanych z moczu, jako wskaznika aktywnosci klebuszkowych zapalen nerek--czy gra jest warta swieczki?

The significance of the native urine sediment in the differential of glomerular disease needs no further comments. However the question arises whether it could be useful to develop a more specific diagnostic approach to identify the origin of renal epithelial cells that can be detected in the urine sediments as well. Especially the detection of podocytes in the urine could be a valuable non-invasive method to get information about the disease activity or disease type and could be used as a follow up. So far there are only a few studies that analyzed the clinicaI relevance of renal epithelial cells in the urine. This review summarizes the available information on marker proteins that have been successfully used in the diagnostic of podocytes in the urine. Furthermore it shows possible diagnostic usefulness of epithelial urinary cells assessment and future research directions.

The clinicopathological determinants of native arteriovenous fistula failure in patients on maintenance hemodialysis.

BACKGROUND: Progressive narrowing of the venous part of dialysis fistulae is caused by hemodynamic and inflammatory factors. OBJECTIVES: The pathogenic and clinical determinants of deterioration of the functioning of arteriovenous fistulae in chronically hemodialyzed patients were evaluated. MATERIAL AND METHODS: The hemodynamic parameters and the activity of inflammatory growth factors in the vessel wall of newly implanted fistulae were assessed and correlated with the clinical course of 34 hemodialyzed patients. Measurements taken at the time of implanting the fistulae included blood flow in the venous part of the anastomosis and its widest diameter by ultrasound Power Doppler, a histopathologic examination of fistula wall samples and measurements of mRNA expression for growth factors PDGFß1 and TGFß in the fistula wall. The results were correlated with clinical data from 36 months' observation: duration of fistula maturation, adequacy of dialysis treatment (eKt/V), the patient's survival, morbidity linked with vascular access problems and general cardiovascular morbidity. RESULTS: The mean duration of fistula maturation was 44.9 days (N = 43, SD = 38.6), whereas the average duration of fistula usage as dialysis access was 795.9 ± 480.6 days. Fistula blood flow at the time of implantation, averaged 1782.2 ± 1735.3 ml/min. The mean number of hospitalization days due to vascular access morbidity was 9.9 ± 15.6 days and it correlated positively with the fistula blood flow (R = 0.596, P = 0.004). There was a negative correlation between the expression of PDGFß1 mRNA and fistula blood flow (R = -0.673, P = 0.011), as well as between TGFß expression and patient survival (R = -0.722, P = 0.002). CONCLUSIONS: Inflammatory activity of the vessel wall growth factors PDGFß1 and TGFß implies impairment of fistula function and the patient's cardiovascular morbidity.

Podocytes in urine, a novel biomarker of preeclampsia?

Preeclampsia is a disorder occurring during pregnancy typically after 20 weeks of gestation. It affects both mother and unborn baby in at least 5-8% of all pregnancies. It is a rapidly progressive condition characterized by high blood pressure and the presence of protein in the urine. The symptoms, such as swelling, sudden weight gain, headaches and vision disturbances, are important signs of preeclampsia which can lead to maternal and infant illness and death. It is estimated that this disorder is responsible for 76,000 maternal and 500,000 infant deaths each year. The main hypothesis explaining the development of preeclampsia is the theory of placental hypoxia/ischemia. An imbalance between vascular endothelial growth factor (VEGF) and soluble fms-like tyro-sine kinase-1 (sFlt-1) seems to play a crucial role. Currently there is no way to predict, with certainty whether preeclampsia will develop during a given pregnancy. There is a need for a diagnostic tool which can help to identify and monitor women at risk. There is growing evidence that podocyturia - urinary excretion of viable podocytes may be a useful predictor of preeclampsia. This paper presents facts supporting such a hypothesis.

Parenchymal injury in remnant-kidney model may be linked to apoptosis of renal cells mediated by nitric oxide.

BACKGROUND: The importance of apoptotic cell death in the pathogenesis of progressive renal sclerosis has been well established. While activity of vasorelaxant nitric oxide is conceivable in the remnant hyperfiltrating kidney and nitric oxide has been reported to cause apoptosis, we postulated that this mechanism of cell death may be operating in progressive renal fibrosis. METHODS: The intensity of apoptosis in glomerular and tubular cells was assessed (light microscopy, TUNEL method) in the remnant-kidney model of progressive renal fibrosis in rats undergoing 5/6 nephrectomy. Numbers of apoptotic cells were correlated with expression of mRNA for inducible nitric oxide synthase (iNOS; RT-PCR in situ), generation of nitrite in renal tissue, an index of glomerulosclerosis, proteinuria and creatinine clearance. A control group of 5/6 nephrectomized rats received an iNOS inhibitor, L-NAME, in drinking water during the 4 weeks after nephrectomy. RESULTS: Number of apoptotic cells gradually increased in experimental rats both in glomeruli and tubules, until termination of the study 3 months after 5/6 nephrectomy. At 3 months postinduction, the intensity of tubular cell apoptosis was significantly correlated with creatinine clearance (p<0.05), while glomerular cell apoptosis was correlated with the index of glomerulosclerosis, also at 3 months (p<0.0025). Along with the apoptosis, the levels of iNOS mRNA for, and generation of, nitrite in renal tissue had risen until termination of the study. The generation of nitrites correlated with the number of apoptotic glomerular cells (p<0.025). Treatment with the iNOS inhibitor resulted in a significant reduction in number of apoptotic cells (p<0.01). CONCLUSIONS: Apoptotic depletion of renal tubular and glomerular cells linked to activity of iNOS may contribute to progression of chronic kidney tissue injury in the 5/6 nephrectomy model.

Discontinuation of mycophenolate mofetil from a tacrolimus-based triple regimen 2 months after renal transplantation: a comparative randomized, multicentre study.

Previous clinical data suggested that with a tacrolimus-based regimen adjunctive immunosuppressives may be withdrawn after an initial treatment period. This study investigated the early discontinuation of mycophenolate mofetil (MMF) from a standard triple regimen. Patients were randomized either to receive a continued tacrolimus/MMF/steroids triple regimen (control group) or to reduce and then stop the MMF dose (MMF stop group). Both groups received identical daily tacrolimus and corticosteroid doses. The initial MMF dose was 1 g/day in both arms, but in the MMF stop group the dose was reduced to 0.5 g/day from week 7 to week 12 and then stopped. The intent-to-treat population consisted of 74 (control) and 78 (MMF stop) patients. MMF was tapered off as planned in 82.9% of the patients in the MMF stop arm. The 6-month incidence of biopsy-proven acute rejection was similar in both arms (21.6% control, 16.7% MMF stop). Graft loss occurred in 5.4% (control) and 3.8% (MMF stop) of the patients. MMF could be safely discontinued from a tacrolimus-based triple therapy early after transplantation without any rebound in efficacy during the 6-month follow-up period. (Name of registry: ClinicalStudyResults.org, number: FG-02-CEE-01, date: 9 June 2006).

[Fabry disease]. / Choroba Fabry'ego.

Fabry disease is a rare genetic disorder, which is linked to a defect of alfa-galactosidase. In consequence it leads to an excess of glicosphyngolipids in lysosomes of various tissues and organs. Clinical symptoms are related to heart, skin, kidneys and nervous system. Nowadays due to a possibility of substitution of galactosidase A, a influence on clinical course of the disease can be attained: arresting of progression and avoidance of complications.