Importance of numerical density of tubulointerstitium infiltrates in the prognosis of antineutrophil cytoplasmic antibodies-associated glomerulonephritis.

AIM: To examine the association of the numerical density of the tubulointerstitium infiltrate with pathohistological changes in the glomeruli and the estimated glomerular filtration rate (eGFR) at kidney biopsy and after 18 months. METHODS: This retrospective study enrolled 44 patients (43.2% male) with antineutrophil cytoplasmic antibodies-associated glomerulonephritis treated at the University Clinical Center of Vojvodina between 2017 and 2020. The numerical density of infiltrates in the tubulointerstitium was determined with the Weibel (M-2) system. Data on biochemical, clinical, and pathohistological parameters were obtained. RESULTS: The mean age was 57.7±10.23 years. Global sclerosis in more than 50% of glomeruli and crescents in more than 50% of glomeruli were significantly associated with a mean lower eGFR (17.6±11.78; 32.0±26.13, respectively) at kidney biopsy (P=0.002; P<0.001, respectively), but not after 18 months. The average numerical density of infiltrates was significantly higher in patients with more than 50% of globally sclerotic glomeruli (P<0.001) and with crescents in more than 50% of glomeruli (P<0.001). The average numerical density of infiltrates significantly correlated with eGFR at biopsy (r=-0.614), but not after 18 months. Our results were confirmed by using multiple linear regression. CONCLUSION: Numerical density of infiltrates, and global glomerular sclerosis and crescents in more than 50% of glomeruli significantly affect eGFR at biopsy, but not after 18 months.

The fractal and textural analysis of glomeruli in obese and non-obese patients.

Background Fractal dimension is an indirect indicator of signal complexity. The aim was to evaluate the fractal and textural analysis parameters of glomeruli in obese and non-obese patients with glomerular diseases and association of these parameters with clinical features. Methods The study included 125 patients mean age 46 ±â€¯15.2 years: obese (BMI ≥ 27 kg/m2-63 patients) and non-obese (BMI < 27 kg/m2-62 patients). Serum concentration of creatinine, protein, albumin, cholesterol, trygliceride, and daily proteinuria were measured. Formula Chronic Kidney Disease Epidemiology Colaboration (CKD-EPI) equation was calculated. Fractal (fractal dimension, lacunarity) and textural (angular second moment (ASM), textural correlation (COR), inverse difference moment (IDM), textural contrast (CON), variance) analysis parameters were compared between two groups. Results Obese patients had higher mean value of variance (t = 1.867), ASM (t = 1.532) and CON (t = 0.394) but without significant difference (P > 0.05) compared to non-obese. Mean value of COR (t = 0.108) and IDM (t = 0.185) were almost the same in two patient groups. Obese patients had higher value of lacunarity (t = 0.499) in comparison with non-obese, the mean value of fractal dimension (t = 0.225) was almost the same in two groups. Significantly positive association between variance and creatinine concentration (r = 0.499, P < 0.01), significantly negative association between variance and CKD-EPI (r = -0.448, P < 0.01), variance and sex (r = -0.339, P < 0.05) were found. Conclusions Variance showed significant correlation with serum creatinine concentration, CKD-EPI and sex. CON and IDM were significantly related to sex. Fractal and textural analysis parameters of glomeruli could become a supplement to histopathologic analysis of kidney tissue.

Gender-specific differences in hemodialysis patients: a multicenter longitudinal study from Serbia.

PURPOSE: The study was undertaken with the aim to determine gender-specific differences in incident hemodialysis (HD) patient and their changes over time. METHODS: The retrospective longitudinal closed cohort study involved 441 incident patients starting HD in 2014 and followed for 1-59 (median 43, IQR 40) months. Demographic, clinical data, treatment characteristics, laboratory findings and outcome were abstracted from the patients' medical records. RESULTS: The relative number of males on HD was about twice that of females throughout the five years investigated. At the beginning of the study, no significant differences were found in the main demographic and clinical characteristics except that diabetes was more often the underlying disease in men than in women. Systolic blood pressure decreased over time significantly more in females than in males. Throughout the study spKt/V was significantly higher in females than in males, but it increased in patients of both genders. There were no gender differences for comorbidities, vascular access and the majority of laboratory findings except for higher serum levels of creatinine and CRP in men than in women. Relatively more females were treated with erythropoiesis stimulating agents and phosphate binders than males. Age and malignancy were selected as significant predictors of mortality for both genders, and, in addition, polycystic kidney disease, serum level of albumin and CRP for men, but spKt/V for women. CONCLUSION: Some significant gender differences were observed throughout, while others appeared during the study but none of them were due to gender inequalities in the applied treatment.

A Prospective Study of Mid-Trimester MCP-1 Levels as a Predictor of Preterm Delivery.

Background: The prevention of preterm delivery (PTD) represents one of the major topics in modern obstetrics. The aim was to design a prospective study and investigate if mid-trimester serum and amniotic fluid levels of MCP-1 could predict the occurence of spontaneous PTD. Methods: The study involved 198 women who underwent genetic amniocentesis and blood sampling in the middle of their trimester. After applying the criteria for inclusion in the study, there were 16 respondents in the study group, and 38 respondents in the control group. Level of MCP-1 in amniotic fluid and serum was measured with commercially available enzyme-linked immunosorbent assays (ELISA) and statistical analysis was conducted. Results: There was no statistically significant difference in serum or amniotic fluid MCP1 levels between PTD and the control groups. Conclusion: The results suggest that MCP-1 is probably not the most relevant marker for predicting PTD. This study provides new normative data for MCP-1 levels in amniotic fluid and maternal sera and is a valuable tool for future diagnostic and comparative studies.

An experience with colistin applied in treatment of imunocompromised patients with peritonitis on peritoneal dialysis.

INTRODUCTION: Immunocompromised patients, such as those with multiple myeloma on peritoneal dialysis, are particularly susceptible to the occurrence of peritonitis. CASE REPORT: We presented a 56-year-old female patient with a 10-year history of multiple myeloma. The patient was on peritoneal dialysis since 2010. During 2012 the patient had the first episode of peritonitis that was successfully managed, but in 2013 the second episode of peritonitis occured. Analysis of dialysate culture and exit site swab revealed the presence of multiresistant Acinetobacter spp., which was susceptible only to colistin. Prompt colistin therapy was administered at the doses of 100,000 units/day during six days, which resulted in complete recovery of the patient, as well as improvement of local abdominal findings. Gram-negative bacteria (genus Acinetobacter) are common causative agents in hospital-acquired infections. Studies confirmed susceptibility of Acinetobacter to colistin, which was also the case with the presented patient. Intravenous administration of colistin resulted in a complete remission of this severe, life-threatening peritonitis. CONCLUSION: Patients with multiple myeloma and renal failure are highly prone to severe life-threatening infections.

Interferon gamma, interleukin 8 and interleukin 10 in serum of patients with the cervical infection and symptoms of the imminent preterm delivery.

INTRODUCTION: Preterm delivery (PTD), defined as a delivery between 24th and 37th completed week, increases the risk of neonatal morbidity and mortality. There is a growing body of evidence that the intrauterine infection as well as cervicovaginal bacterial infections and Chlamydia infections are possible causes of preterm delivery. Host response to cervicovaginal and/or intrauterine infections is coupled with a release of various inflammatory mediators, many of which are cytokines. OBJECTIVE: The aim of the study was to find out if cervical infection influenced the serum levels of interferon-gamma (IFN-gamma), interleukin 8 (IL-8) and interleukin 10 (IL-10) in patients with the clinical symptoms of the imminent preterm delivery. METHODS: A total of 128 pregnant women (from 24 to 30 weeks of gestation) with the clinical symptoms of the imminent preterm delivery were divided in: study group--85 patients with the cervical infection, and control group--43 patients without the cervical infection. The level of cytokines in the serum was measured with commercial ELISA tests. RESULTS: No significant difference could be found in serum levels of IFN-gamma (p = 0.632), IL-8 (p = 0.712) and IL-10 (p = 0.676) between these two investigated groups. CONCLUSION: The results of our study suggest that there is no significant difference in serum IFN-gamma, IL-8 and IL-10 concentrations between pregnant women with the symptoms of the imminent preterm delivery who had and had no cervical infection.

[Etanercept therapy in rheumatoid arthritis: efficacy and safety].

INTRODUCTION: Etanercept, tumor necrosis factor (TNF-alpha) antagonist, lowers the disease activity level in patients with rheumatoid arthritis (RA), reduces joint destruction saving physical functions and improving life quality. OBJECTIVE: The aim of this study was to establish efficacy and safety of etanercept in combination with disease modifying antirheumatic drugs (DMARDs) in the treatment of RA. METHODS: To patients with active RA, who were on therapy with DMARD, etanercept was introduced in weekly doses of 50 mg, with continuation of DMARD. Efficacy of this form of treatment was evaluated in the 12th week. Maintenance of the effect of treatment was also evaluated during 24, 48 and 96 weeks. Long-term evaluation of etanercept safety was assessed by registering all unwanted events during a two-year period. RESULTS: After 12 weeks of treatment with etanercept, 80% of patients had ACR20 response, while 85% showed clinically significant decrease of DAS28 index. We achieved remission in five patients (12.5%) and low activity of RA in 17 patients (42.5%). During a 96-week of follow-up period, achieved therapy effects were maintained. In four patients (10%) etanercept therapy was interrupted after 24 weeks because of inadequate response. In one of them (2.5%) we recorded a cardiovascular incident. Acute infections were registered in 47 cases. Four of those were severe infections. Neither cases of malignancy development were noted, nor were there any lethal disease outcomes. CONCLUSION: Etanercept in combination with DMARD shows a high level of efficacy in the treatment of RA. The safety profile of the drug is satisfactory.

[Early continuous dialysis in acute glyphosate-surfactant poisoning].

INTRODUCTION: Treating severe acute glyphosate-surfactant poisoning requires intensive therapy including dialysis. Cases of hemoperfusion and hemodialysis use in renal failure induced by herbicide ingestion have been reported in the current medical literature. We present a case report of successful patient treatment with continuous venovenous hemodiafiltration in acute glyphosate-surfactant poisoning. CASE OUTLINE: A 36-year-old male patient attempted suicide by drinking approximately 300 ml of glyphosate-surfactant about an hour before coming to our Clinic. On admittance the patient was somnolent, normotensive, acidotic and hyperkalemic. Six hours after poison ingestion there was no positive response to symptomatic and supportive therapy measures. The patient became hypotensive, hypoxic with oliguric acute renal failure, so that post-dilution continuous veno-venous hemodiafiltration was started. During the treatment the patient became hemodinamically stabile, diuresis was established along with electrolyte and acid-base status correction and a gradual decrease of blood urea nitrogen and creatinine levels. After a single 27.5-hour treatment, clinical condition and renal function parameters did not require further dialysis. Complete recovery of renal function was achieved on the fifth day. CONCLUSION: Early introduction of continuous veno-venous hemodiafiltration with other intensive therapy measures led to complete recovery in a hemodinamically instable patient.

[Therapy of lupus nephritis with mycophenolate mofetil].

INTRODUCTION: Mycophenolate mofetil is an immunosuppressive agent used in transplantation and subsequently in a variety of autoimmune conditions. It inhibits both B and T lymphocyte proliferation, and also has nonimmune effects on the kidney. The major experience in systemic lupus erythematosus has focused on proliferative lupus nephritis. MATERIALS AND METHODS: In our study we treated 8 female patients having proliferative lupus nephritis with combination therapy of prednisone (1 mg/kg body weight) and mycophenolate mofetil (2 g per day). Complete remission was defined as a value for urinary protein excretion that was less than 0.5 g per 24 hours, with normal urinary sediment, a normal serum albumin concentration and improved or stable serum creatinine. Partial remission was defined as a daily proteinuria below 2g in the previously nephrotic patient or minimum 30% from starting values, with normal urinary sediment, serum albumin of minimum 30 g/L and stable serum creatinine. RESULTS: Two patients had a complete remission after 7 and 2 months respectively. Five patients had a partial remission after 5.2 +/- 4.3 months of therapy. One patient did not react to therapy. There were no side effects during the course of therapy. DISCUSSION: Considering the fact that 7/8 patients have had nephrotic range proteinuria and that 50% of patients were refractory on standard induction therapy, the results of this study are a good indicator of value of mycophenolate mofetil in the therapy of proliferative forms of lupus nephritis. CONCLUSION: Mycophenolate mofetil has satisfactory results in the treatment of proliferative forms of lupus nephritis with minimal side effects.

[Evaluation of effects of the intravenous cyclophosphamide treatment of primary glomerulonephritis and the estimation of complications].

INTRODUCTION: Primary glomerulonephritis can be treated by the intravenous use of cyclophosphamide. The aim of our study is to evaluate the effect of the drug in the treatment of mentioned diseases and the follow-up of complications. MATERIAL AND METHODS: There are 30 patients included in this study, mean-age of 46.83 years. Renal biopsy was performed in 25 patients. Membranoproliferative glomerulonephritis was diagnosed in 36.67% of patients, mesangioproliferative in 16.67%, rapidly progressive in 13,33%, membranous in 10%, chronic in 10%, primary focal segmental glomerulosclerosis in 3,33% and 10% of patients were unclassified They have been treated with cyclophosphamide in intermittent "pulse" doses: once a month fbr the first 6 months and once in 3 months, for 18 months or longer, after that. RESULTS AND DISCUSSION: The drug was given in the recommended dose of 0.5-lg/m of body-surface area, in the combination with a low-dose corticosteroides. Hematological and renal fimnctional tests were checked before every "pulse" dose. Concerning the development of the renal ailure the fivorable effect occurred in 50% of patients. Proteinuria was found in all patients (80% >3.5 gr/24 h). The favorable effect occurred in 80% patients. At the end, serum proteins were normal in 76.67% patients. 30% of patients normalized the erythrocyte sedimentation level. Remission has not been achieved in 23.33% of patients, 10% of patients developed relapse. 20% of patients died infections were the most common complication and they occurred in 30% of patients. Sepsis, leucopenia, Herpes Zoster infection and hemorrhagic cystitis have not occurred in any patient. Malignant tumor was found in 6.67% of patients.

[Therapy of lupus nephritis with mycophenolate mofetil].

INTRODUCTION: Mycophenolate mofetil is an immunosupressive agent used in transplantation and subsequently in a variety of autoimmune conditions. It inhibits both B and T lymphocyte proliferation, and also has nonimmune effects on the kidney. The major experience in systemic lupus erythematosus has focused on proliferative lupus nephritis. MATERIALS AND METHODS: In our study we treated 8 female patients with proliferative lupus nefritis with combination therapy of prednisone (1 mg/kg body weight) and mycophenolate mofetil (2 g per day). Complete remission was defined as a value for urinary protein excretion that was less than 0.5 g per 24 hours, with normal urinary sediment, a normal serum albumin concentration and improved or stable serum creatinine. Partial remission was defined as a daily proteinuria below 2 g in a previously nephrotic patient or minimum 30% from starting values, with normal urinary sediment, serum albumin of minimum 30 g/L and stable serum creatinine. RESULTS: Two patients had a complete remission after 7 and 2 months respectively. Five patients had a partial remission after 5.2+/-4.3 months of therapy. One patient did not react on therapy. There were no side effects during the course of therapy. DISCUSSION: Considering the fact that 7/8 patients have had nephrotic range proteinuria and that 50% of patients were refractory on standard induction therapy, results of this study are good indicator of value of mycophenolate mofetil in the terapy of proliferative forms of lupus nephritis. CONCLUSION: Mycophenolate mofetil gives satisfactory results in the treatment of proliferative forms of lupus nephritis with minimal side effects.

[Long term survival of patients with lupus nephritis]. / Dugogodisnje prezivljavanje bolesnika s lupusnim nefritisom.

Lupus nephritis is a clinical manifestation of Systemic Lupus Erythematosus with most prominent influence on the course of the disease. The most predictive parameters for development of renal failure are: type of hystological changes, degree of interstitial inflammation, serum creatinine concentration at the time of diagnosis and therapeutical protocols used in the treatment. Single center experience in a group of 220 lupus patients is presented in this paper. In 130 patients (59%) lupus nephritis was diagnosed by clinical and laboratory tests, while 74 kidney biopsies were performed. Proliferative type of lupus nephritis (class IV in 54% of cases and class III in 18.9%) was more frequent than the other histological types. During a long term follow up (range 1-17 years, mean 7.6 years) renal failure developed in 17 patients (24%), while 11% of patients developed uremia and required dialysis. Development of renal failure was influenced by histological changes with predominance of class IV lupus nephropathy, disseminated disease with more ARA criteria for systemic lupus erythematosus classification present at the time of kidney biopsy, more frequent lupus flares, persistence of low complement levels during the first year of follow-up and even earlier.