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Our study included 41 patients fulfilling the Milan criteria preoperatively and aimed to identify individuals at high risk of post-resection HCC relapse, which occurred in 18 out of 41 patients (43.9%), retrospectively. We analyzed whole slide images of CD8 immunohistochemistry with automated segmentation of tissue classes and detection of CD8+ lymphocytes. The image analysis outputs were subsampled using a hexagonal grid-based method to assess spatial distribution of CD8+ lymphocytes with regards to the epithelial edges. The CD8+ lymphocyte density indicators, along with clinical, radiological, post-surgical and pathological variables, were tested to predict HCC relapse. Low standard deviation of CD8+ density along the tumor edge and R1 resection emerged as independent predictors of shorter recurrence-free survival (RFS). In particular, patients presenting with both adverse predictors exhibited 100% risk of relapse within 200 days. Our results highlight the potential utility of integrating CD8+ density variability and surgical margin to identify a high relapse-risk group among Milan criteria-fulfilling HCC patients. Validation in cohorts with core biopsy could provide CD8+ distribution data preoperatively and guide preoperative decisions, potentially prioritizing liver transplantation for patients at risk of incomplete resection (R1) and thereby improving overall treatment outcomes significantly. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is widely recognized as a precursor to the onset or rapid progression of chronic kidney disease (CKD). However, there is currently no effective treatment available for AKI, underscoring the urgent need for the development of new strategies to improve kidney function. Human placental mesenchymal stromal cells (hpMSCs) were isolated from donor placentas, cultured, and characterized with regard to yield, viability, flow cytometry, and potency. To mimic AKI and its progression to CKD in a rat model, a dedicated sensitive non-clinical bilateral kidney ischemia-reperfusion injury (IRI) model was utilized. The experimental group received 3 × 105 hpMSCs into each kidney, while the control group received IRI and saline and the untreated group received IRI only. Urine, serum, and kidney tissue samples were collected over a period of 28 days. The hpMSCs exhibited consistent yields, viability, and expression of mesenchymal lineage markers, and were also shown to suppress T cell proliferation in a dose-dependent manner. To ensure optimal donor selection, manufacturing optimization, and rigorous quality control, the rigorous Good Manufacturing Practice (GMP) conditions were utilized. The results indicated that hpMSCs increased rat survival rates and improved kidney function by decreasing serum creatinine, urea, potassium, and fractionated potassium levels. Furthermore, the study demonstrated that hpMSCs can prevent the initial stages of kidney structural fibrosis and improve kidney function in the early stages by mitigating late interstitial fibrosis and tubular atrophy. Additionally, a robust manufacturing process with consistent technical parameters was established. [ABSTRACT FROM AUTHOR]

Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette–Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial–stromal interface zone compartments and their distribution, represented by an epithelial–stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012, p-value = 0.0002), CD8 (HR: 0.0379, p-value = 0.005), and ICOS (HR: 0.0768, p-value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93, p-value = 0.0001) and T1 tumor stage (HR: 2.04, p-value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83, p-value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

The limited reproducibility of the grading of non-muscle invasive papillary urothelial carcinoma (NMIPUC) necessitates the search for more robust image-based predictive factors. In a cohort of 157 NMIPUC patients treated with Bacille Calmette–Guérin (BCG) immunotherapy, we explored the multiple instance learning (MIL)-based classification approach for the prediction of 2-year and 5-year relapse-free survival and the multiple instance survival learning (MISL) framework for survival regression. We used features extracted from image patches sampled from whole slide images of hematoxylin–eosin-stained transurethral resection (TUR) NPMIPUC specimens and tested several patch sampling and feature extraction network variations to optimize the model performance. We selected the model showing the best patient survival stratification for further testing in the context of clinical and pathological variables. MISL with the multiresolution patch sampling technique achieved the best patient risk stratification (concordance index = 0.574, p = 0.010), followed by a 2-year MIL classification. The best-selected model revealed an independent prognostic value in the context of other clinical and pathologic variables (tumor stage, grade, and presence of tumor on the repeated TUR) with statistically significant patient risk stratification. Our findings suggest that MISL-based predictions can improve NMIPUC patient risk stratification, while validation studies are needed to test the generalizability of our models. [ABSTRACT FROM AUTHOR]

Simple Summary: Prognosis of patients after surgical resection for hepatocellular carcinoma (HCC) is often obscured by the variable impact of the tumor and remaining liver properties. We applied a convolutional neural network and hexagonal grid analytics to extract prognostic indicators from collagen microarchitecture within the tumor and adjacent liver tissue. By associating the extracted features from two distinct fiber types with clinical outcomes, we have developed two computational models to predict the overall survival of the patients. We report the independent prognostic roles for reticulin in HCC and fibrillary collagen in the peritumoral liver, highlighting the significance of assessing region-specific and type-specific fiber features. Our study provides evidence that the predictive power of prognostic models of HCC can be enhanced by artificial intelligence solutions generating computational image-based biomarkers. Despite advances in diagnostic and treatment technologies, predicting outcomes of patients with hepatocellular carcinoma (HCC) remains a challenge. Prognostic models are further obscured by the variable impact of the tumor properties and the remaining liver parenchyma, often affected by cirrhosis or non-alcoholic fatty liver disease that tend to precede HCC. This study investigated the prognostic value of reticulin and collagen microarchitecture in liver resection samples. We analyzed 105 scanned tissue sections that were stained using a Gordon and Sweet's silver impregnation protocol combined with Picric Acid–Sirius Red. A convolutional neural network was utilized to segment the red-staining collagen and black linear reticulin strands, generating a detailed map of the fiber structure within the HCC and adjacent liver tissue. Subsequent hexagonal grid subsampling coupled with automated epithelial edge detection and computational fiber morphometry provided the foundation for region-specific tissue analysis. Two penalized Cox regression models using LASSO achieved a concordance index (C-index) greater than 0.7. These models incorporated variables such as patient age, tumor multifocality, and fiber-derived features from the epithelial edge in both the tumor and liver compartments. The prognostic value at the tumor edge was derived from the reticulin structure, while collagen characteristics were significant at the epithelial edge of peritumoral liver. The prognostic performance of these models was superior to models solely reliant on conventional clinicopathologic parameters, highlighting the utility of AI-extracted microarchitectural features for the management of HCC. [ABSTRACT FROM AUTHOR]

Introduction The diagnosis of glomerular diseases is primarily based on visual assessment of histologic patterns. Semi-quantitative scoring of active and chronic lesions is often required to assess individual characteristics of the disease. Reproducibility of the visual scoring systems remains debatable, while digital and machine-learning technologies present opportunities to detect, classify and quantify glomerular lesions, also considering their inter- and intraglomerular heterogeneity. Materials and methods: We performed a cross-validated comparison of three modifications of a convolutional neural network (CNN)-based approach for recognition and intraglomerular quantification of nine main glomerular patterns of injury. Reference values provided by two nephropathologists were used for validation. For each glomerular image, visual attention heatmaps were generated with a probability of class attribution for further intraglomerular quantification. The quality of classifier-produced heatmaps was evaluated by intersection over union metrics (IoU) between predicted and ground truth localization heatmaps. Results: A proposed spatially guided modification of the CNN classifier achieved the highest glomerular pattern classification accuracies, with area under curve (AUC) values up to 0.981. With regards to heatmap overlap area and intraglomerular pattern quantification, the spatially guided classifier achieved a significantly higher generalized mean IoU value compared to single-multiclass and multiple-binary classifiers. Conclusions: We propose a spatially guided CNN classifier that in our experiments reveals the potential to achieve high accuracy for the localization of intraglomerular patterns. [ABSTRACT FROM AUTHOR]

Simple Summary: Bacille Calmette–Guerin (BCG) immunotherapy of non-muscle invasive papillary urothelial carcinoma fails in over 30% of cases. In our study, we explore the significance of tumor-infiltrating cytotoxic lymphocytes, assessed by digital analysis and computational methods measuring the cell gradient density profiles across the tumor epithelium–stroma interface, to predict recurrence-free survival in these patients. We analyzed CD8+ cell distribution profiles in the tumor tissue using previously published methods of gradient assessment (center of mass and immunodrop) along with patients' clinical and pathology data. We found that both CD8+ cell gradient indicators were statistically significant prognosticators of recurrence-free survival, and together with clinical and pathological data might be used for improved patient risk stratification. In this context, we propose a prototypic risk assessment system incorporating pathology, patients' history, and CD8+ cell gradient features. Background: Bacille Calmette–Guerin (BCG) immunotherapy is the first-line treatment in patients with high-risk non-muscle invasive papillary urothelial carcinoma (NMIPUC), the most common type of bladder cancer. The therapy outcomes are variable and may depend on the immune response within the tumor microenvironment. In our study, we explored the prognostic value of CD8+ cell density gradient indicators across the tumor epithelium–stroma interface of NMIPUC. Methods: Clinical and pathologic data were retrospectively collected from 157 NMIPUC patients treated with BCG immunotherapy after transurethral resection. Whole-slide digital image analysis of CD8 immunohistochemistry slides was used for tissue segmentation, CD8+ cell quantification, and the assessment of CD8+ cell densities within the epithelium–stroma interface. Subsequently, the gradient indicators (center of mass and immunodrop) were computed to represent the density gradient across the interface. Results: By univariable analysis of the clinicopathologic factors, including the history of previous NMIPUC, poor tumor differentiation, and pT1 stage, were associated with shorter RFS (p < 0.05). In CD8+ analyses, only the gradient indicators but not the absolute CD8+ densities were predictive for RFS (p < 0.05). The best-performing cross-validated model included previous episodes of NMIPUC (HR = 4.4492, p = 0.0063), poor differentiation (HR = 2.3672, p = 0.0457), and immunodrop (HR = 5.5072, p = 0.0455). Conclusions: We found that gradient indicators of CD8+ cell densities across the tumor epithelium–stroma interface, along with routine clinical and pathology data, improve the prediction of RFS in NMIPUC. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we present the overall survival and recurrence-free survival models based on CD8 profiles in hepatocellular carcinoma (HCC) and peritumoral liver tissue, including other clinical and pathological variables. We extracted CD8 distribution profiles from the digitized immunohistochemistry slides containing the HCC-stroma interface and the perineoplastic liver parenchyma-stroma interface using the computational method of interface zone immunogradient. The prognostic value of the CD8+ cell spatial distribution indicators from both interfaces as well as clinical, laboratory, and pathology data was assessed. A three-tier prognostic scoring system is proposed to predict overall survival in patients with HCC. Hepatocellular carcinoma (HCC) often emerges in the setting of long-standing inflammatory liver disease. CD8 lymphocytes are involved in both the antitumoral response and hepatocyte damage in the remaining parenchyma. We investigated the dual role of CD8 lymphocytes by assessing density profiles at the interfaces of both HCC and perineoplastic liver parenchyma with surrounding stroma in whole-slide immunohistochemistry images of surgical resection samples. We applied a hexagonal grid-based digital image analysis method to sample the interface zones and compute the CD8 density profiles within them. The prognostic value of the indicators was explored in the context of clinicopathological, peripheral blood testing, and surgery data. Independent predictors of worse OS were a low standard deviation of CD8+ density along the tumor edge, high mean CD8+ density within the epithelial aspect of the perineoplastic liver-stroma interface, longer duration of surgery, a higher level of aspartate transaminase (AST), and a higher basophil count in the peripheral blood. A combined score, derived from these five independent predictors, enabled risk stratification of the patients into three prognostic categories with a 5-year OS probability of 76%, 40%, and 8%. Independent predictors of longer RFS were stage pT1, shorter duration of surgery, larger tumor size, wider tumor-free margin, and higher mean CD8+ density in the epithelial aspect of the tumor-stroma interface. We conclude that (1) our computational models reveal independent and opposite prognostic impacts of CD8+ cell densities at the interfaces of the malignant and non-malignant epithelium interfaces with the surrounding stroma; and (2) together with pathology, surgery, and laboratory data, comprehensive prognostic models can be constructed to predict patient outcomes after liver resection due to HCC. [ABSTRACT FROM AUTHOR]

Cerium and chromium co-doped gadolinium aluminum gallium garnets were prepared using sol-gel technique. These compounds potentially can be applied for NIR-LED construction, horticulture and theranostics. Additionally, magnesium and calcium ions were also incorporated into the structure. X-ray diffraction data analysis confirmed the all-cubic symmetry with an Ia-3d space group, which is appropriate for garnet-type materials. From the characterization of the luminescence properties, it was confirmed that both chromium and cerium emissions could be incorporated. Cerium luminescence was detected under 450 nm excitation, while for chromium emission, 270 nm excitation was used. The emission of chromium ions was exceptionally intense, although it was determined that these compounds are doped only by parts per million of Cr3+ ions. Typically, the emission maxima of chromium ions are located around 650–750 nm in garnet systems. However, in this case, the emission maximum for chromium is measured to be around 790 nm, caused by re-absorption of Cr3+ ions. The main observation of this study is that the switchable emission wavelength in a compound of single phase was obtained, despite the fact that doping with Cr ions was performed in ppm level, causing an intense emission in NIR region. [ABSTRACT FROM AUTHOR]

Simple Summary: For pathologists, how to precisely diagnose cancer from microscopy slides of tumor tissue samples so that each patient may receive the optimal treatment for his specific type of disease is a major task. Recent research based on digital pathology image analysis enables new approaches to assess tumor-host interaction at a microscopic level. The current study applies a novel spatial analysis method which computes Immunogradient indicators to estimate the migration of immune cells towards the tumor across the tumor/stroma interface. These indicators, computed for two types of immune cells (CD8 and CD20), proved to be independent prognostic factors in this study of 87 patients with colorectal cancer. The indicators were combined with infiltrative tumor growth pattern, assessed by a pathologist, into a new immuno-interface score which enabled prediction of the patient survival independent of other clinical, pathology and molecular characteristics of the tumor. The study demonstrates the value of computational pathology to advance the precision of clinical decision-making. Tumor-associated immune cells have been shown to predict patient outcome in colorectal (CRC) and other cancers. Spatial digital image analysis-based cell quantification increases the informative power delivered by tumor microenvironment features and leads to new prognostic scoring systems. In this study we evaluated the intratumoral density of immunohistochemically stained CD8, CD20 and CD68 cells in 87 cases of CRC (48 were microsatellite stable, MSS, and 39 had microsatellite instability, MSI) in both the intratumoral tumor tissue and within the tumor-stroma interface zone (IZ) which was extracted by a previously developed unbiased hexagonal grid analytics method. Indicators of immune-cell gradients across the extracted IZ were computed and explored along with absolute cell densities, clinicopathological and molecular data, including gene mutation (BRAF, KRAS, PIK3CA) and MSI status. Multiple regression modeling identified (p < 0.0001) three independent prognostic factors: CD8+ and CD20+ Immunogradient indicators, that reflect cell migration towards the tumor, were associated with improved patient survival, while the infiltrative tumor growth pattern was linked to worse patient outcome. These features were combined into CD8-CD20 Immunogradient and immuno-interface scores which outperformed both tumor-node-metastasis (TNM) staging and molecular characteristics, and importantly, revealed high prognostic value both in MSS and MSI CRCs. [ABSTRACT FROM AUTHOR]

Thermally reduced graphene oxide (TRGO) is a graphene-based nanomaterial that has been identified as promising for the development of amperometric biosensors. Urease, in combination with TRGO, allowed us to create a mediator-free amperometric biosensor with the intention of precise detection of urea in clinical trials. Beyond simplicity of the technology, the biosensor exhibited high sensitivity (2.3 ± 0.1 µA cm−2 mM−1), great operational and storage stabilities (up to seven months), and appropriate reproducibility (relative standard deviation (RSD) about 2%). The analytical recovery of the TRGO-based biosensor in urine of 101 ÷ 104% with RSD of 1.2 ÷ 1.7% and in blood of 92.7 ÷ 96.4%, RSD of 1.0 ÷ 2.5%, confirmed that the biosensor is acceptable and reliable. These properties allowed us to apply the biosensor in the monitoring of urea levels in samples of urine, blood, and spent dialysate collected during hemodialysis. Accuracy of the biosensor was validated by good correlation (R = 0.9898 and R = 0.9982) for dialysate and blood, utilizing approved methods. The advantages of the proposed biosensing technology could benefit the development of point-of-care and non-invasive medical instruments. [ABSTRACT FROM AUTHOR]

Despite advances in diagnostic and treatment technologies, predicting outcomes of patients with hepatocellular carcinoma (HCC) remains a challenge. Prognostic models are further obscured by the variable impact of the tumor properties and the remaining liver parenchyma, often affected by cirrhosis or non-alcoholic fatty liver disease that tend to precede HCC. This study investigated the prognostic value of reticulin and collagen microarchitecture in liver resection samples. We analyzed 105 scanned tissue sections that were stained using a Gordon and Sweet's silver impregnation protocol combined with Picric Acid-Sirius Red. A convolutional neural network was utilized to segment the red-staining collagen and black linear reticulin strands, generating a detailed map of the fiber structure within the HCC and adjacent liver tissue. Subsequent hexagonal grid subsampling coupled with automated epithelial edge detection and computational fiber morphometry provided the foundation for region-specific tissue analysis. Two penalized Cox regression models using LASSO achieved a concordance index (C-index) greater than 0.7. These models incorporated variables such as patient age, tumor multifocality, and fiber-derived features from the epithelial edge in both the tumor and liver compartments. The prognostic value at the tumor edge was derived from the reticulin structure, while collagen characteristics were significant at the epithelial edge of peritumoral liver. The prognostic performance of these models was superior to models solely reliant on conventional clinicopathologic parameters, highlighting the utility of AI-extracted microarchitectural features for the management of HCC.

Introduction: Many theories have been proposed to explain pathogenesis of COPD; however, remains unclear why the majority of smokers (~80%) do not develop COPD, or only develop a mild disease. To explore if COPD has an autoimmune component, the role of T regulatory lymphocytes (Tregs) in the lung tissue of COPD patients is of crucial importance., Material and Methods: Bronchial tissue biopsy samples were prospectively collected from 64 patients (39 COPD and 25 controls - 15 smokers and 10 non-smokers). The patients with COPD were subdivided into mild/moderate (GOLD stage I-II) and severe/very severe (GOLD stage III-IV) groups. Digital image analysis was performed to estimate densities of CD4+ CD25+ cell infiltrates in double immunohistochemistry slides of the biopsy samples. Blood samples were collected from 42 patients (23 COPD and 19 controls) and tested for CD3+ CD4+ CD25+ bright lymphocytes by flow cytometry., Results: The number of intraepithelial CD4+ CD25+ lymphocytes mm-2 epithelium was significantly lower in the severe/very severe COPD (GOLD III-IV) group as well as in the control non-smokers (NS) group (p < 0,0001). Likewise, the absolute number of Treg (CD3+ CD4+ CD25+ bright) cells in the peripheral blood samples was significantly different between the four groups (p = 0.032). The lowest quantity of Treg cells was detected in the severe/very severe COPD and healthy non-smokers groups., Conclusion: Our findings suggest that severe COPD is associated with lower levels of Tregs in the blood and bronchial mucosa, while higher Tregs levels in the smokers without COPD indicate potential protective effect of Tregs against developing COPD.

Unlabelled: Fabry's disease is an X-linked inborn error of glycosphingolipid metabolism caused by a deficiency of the lysosomal hydrolase alpha-galactosidase A. Due to deficiency of this enzyme activity, a progressive lysosomal accumulation of glycosphingolipids, in particular globotriaosylceramide, takes place within endothelial cells and cells of the vascular and nervous systems, myocardial cells, endothelial, and mesangial and epithelial cells of the kidney, eventually leading to organ dysfunction. The degree of renal involvement generally correlates with the progression of glycosphingolipid accumulation and may lead to renal insufficiency and failure. Renal dysfunction can progress to end-stage renal failure, which usually occurs in the third to fifth decade of life. The prevalence of this disease among males on chronic hemodialysis is different in various countries. Screening for alpha-galactosidase A deficiency by blood spot tests was performed among 536 male dialysis patients in all 42 hemodialysis centers in Lithuania in the period of April-June, 2005. All tests, showed normal galactosidase A enzymatic activity., Conclusion: No patient with suspicion of Fabry's disease was found by this screening method.

A retrospective study of 1363 native kidney biopsies, performed at Lithuanian nephrology units and investigated at the National Center of Pathology during the period of 2000-2006, was carried out. Inflammatory glomerulopathies constituted 63.6% of all primary glomerulopathies (834 cases); IgA nephropathy was the most frequent disease (35.0%). The incidence of membranoproliferative glomerulonephritis decreased from 22.6% reported in Lithuania previously (1995-1999) to 16.7% in this study; however, it was still higher compared to most European countries. Extracapillary proliferative glomerulonephritis and diffuse endocapillary proliferative glomerulonephritis accounted for 9.1% and 4.4%, respectively. Noninflammatory glomerulopathies were relatively rare: focal and segmental glomerulosclerosis made up 14.8%; minimal change disease, 9.7%; membranous nephropathy, 7.4%. However, their incidence increased compared to the previously reported in 1995-1999 (9.5%, 5.8%, and 4.3%, respectively). It can be concluded that inflammatory glomerulopathies were predominant in Lithuania in 2000-2006; however, these glomerulopathies were less prominent as compared to the previously reported data in 1995-1999.

Objective: To delineate technical aspects of vascular models with intracranial aneurysm in vitro production, suitable for angiographic imaging., Material and Methods: Wax (K2 exact, S-U-CERAMO-CAPS-WAX), Girtl's mass, gelatin, and silicone (Silicone 10015 Den Braven, Elastosil 7683/25, Elite Double 32 Shore-A, Rema-Sil) were used for model production. Construction of models was based on T-shaped plastic tube connections and lost core techniques. Images of rotational angiography, glass tubes with aneurysm, and casts obtained in human specimen were used as samples of cerebral arteries., Results: Technical aspects of vascular models production were delineated in experience of eight silicone models produced. M1 was hand made with basilar tip aneurysm; M2 was obtained according to angiography images with internal carotid artery supraclinoid part bifurcation to anterior and middle cerebral artery aneurysm. BM1 and BM2 casts were made using glass tubes with lateral aneurysm, M3--from T-shaped plastic tubes with lateral aneurysms. M4, M5, and M6 were formed using casts obtained in human specimen with basilar tip aneurysm., Conclusions: Silicone of two components is practical for casts of cerebral arteries in human specimen production. Gelatinous solution 50 degrees C diluted 1:1 with water can be used for copies of arterial casts production. Wax materials are unsuitable for making casts in a human specimen.

Unlabelled: The pathogenesis of an immune complex-mediated membranoproliferative glomerulonephritis (IMPGN) involves persistent deposition of circulating immune complexes in the glomeruli caused by persistent antigenemia. We have previously reported relatively high incidence of IMPGN in Lithuania. The objective of our study was to evaluate potential causes of persistent antigenemia in the patients with IMPGN., Material and Methods: Forty-five patients with IMPGN diagnosed on renal biopsy during 2000-2002 were retrospectively evaluated for the presence of persistent bacterial or viral infections, autoimmune diseases and other associated medical conditions. Patients with established diagnosis of systemic lupus erythematosus (SLE) before the biopsy were not included in the study., Results: A great majority (20; 44%) of the patients were found to have persistent bacterial infections of various localization. Four patients (9%) were infected with hepatitis B virus (HBV). Three (7%) patients were eventually diagnosed with SLE and another 3 (7%) had other associated pathology. In the remaining 15 (33%) patients, IMPGN remained idiopathic. Testing for hepatitis C virus (HCV) antibody was performed in 36 patients (12 of them with idiopathic IMPGN) and was negative in all patients. Testing for HCV RNA was not performed. Patients with bacterial infections were significantly younger compared to the group of idiopathic IMPGN (36.5+/-19.1 and 53.8+/-16.4, respectively, p=0.01). We conclude that persistent bacterial infection was a major potential source of antigenemia in our patients with IMPGN, particularly in the younger patients, while HBV and HCV infection was rarely detected.

Two hundred eighty patients underwent renal biopsy during the period of 1995-1999 in five nephrological centers of Lithuania. All renal biopsies materials were examined in the State Center of Pathology. In 20 patients (7.1%) membranous nephropathy was found. The main clinical presentation at the moment of renal biopsy were nephrotic syndrome (55%) and arterial hypertension (55%). Glomerulosclerosis was found in 30% of patients, interstitial fibrosis--in 40% of patients. The results of analysis showed multiple risk factors for renal failure progression: initial renal failure (p=0.000), systolic and diastolic hypertension (p=0.009 and p=0.009), proteinuria (=1 g/l, =3 g/l) (p=0.026). Membranous nephropathy was found to have a relatively good long-term prognosis - the renal survival rate in 5 years was 84.2%. Kaplan-Meier survival analysis showed that initial renal failure was risk factor (logrank p=0.018, Breslov p=0.032) associated with development of end-stage renal disease in 5 years.

Cyclosporin A (CsA) is an effective immunosuppressive drug for the prophylaxis of rejection after organ transplantation. However, CsA is potentially toxic to various tissues: kidney, liver, pancreas, nervous system, etc. The aim of this study was to ascertain the frequency of CsA nephrotoxicity incidence according to the changes in graft biopsy material and its association with whole blood CsA levels. Data were obtained from 30 recipients after cadaver or living related kidney transplantation. All patients (pts) were divided into two groups: Gr1 included 17 pts with biopsy evidence of CsA damage and Gr2 -13 pts without these changes. The mean age of recipients (38.6+/-11.3 vs 34.6+/-13.3), donor and recipient human leucocyte antigen (HLA) match (2.5/6 vs 2.3/6), cold ischemic time (12.0+/- 9.3 h vs 13.8+/-10.3 h), percentage of kidney from cadaver donors (64.7% vs 69.2%) were similar in both groups. Comparison of CsA blood levels (>200 ng/ml) between Gr1 and Gr2 revealed statistically significant differences (70.6% vs 15.4%, p<0.05), correspondingly. The mean CsA blood level was higher in Gr1 (328.7+/-153.8 ng/ml vs 202.4+/-145.6 ng/ml, p<0.03). Thus, we suggest that CsA nephrotoxicity is associated with elevated CsA levels of more than 200 ng/ml. Biopsy is a very important criteria that helps to distinguish CsA nephrotoxicity and acute rejection.

A retrospective study of 316 patients, who underwent renal biopsy, during the period of 1995-1999 in five nephrological centers of Lithuania. All renal biopsy materials were investigated in the State Center of Pathology. Male:female ratio was 204:112, the mean age 41.4 (SD 16.7) yrs., range 15-80. The main indications for renal biopsy were nephrotic syndrome (29.1%), hematuria and nonnephrotic proteinuria (27.8%). The leading type of kidney damage was primary glomerulonephritis--194 (69.3%), which was 2.4 times more frequent in males than in females. The dominant types of primary glomerulonephritis were IgA nephropathy--30.4%, membranoproliferative glomerulonephritis--26.8%, membranous nephropathy--10.3% and focal segmental glomerulosclerosis--9.8%. Renal amyloidosis was found even in 8.6% of all renal biopsies.