Case Report: Silicosis and IgA nephropathy, an exceptional association

A 57-year-old male who had been working in masonry for 33 years was hospitalized for renal function decline associated with exertional dyspnea. He presented with hypertension and limb edema. Urinalysis revealed an active urine sediment with glomerular proteinuria at 1.5 g/24h and the renal biopsy identified mesangial IgA Nephropathy. Chest tomography scans showed signs of silicosis. The patient received Angiotensin-Converting Enzyme Inhibitors with stable renal function. To our knowledge, the association of silicosis-IgA nephropathy has rarely been reported in the literature. This case highlights the effect of chronic exposure to silica dust and its association with both silica and renal disease.

An Interesting Case of Nonlupus Full-House Nephropathy

Full-house immunofluorescence and endothelial tubuloreticular inclusions are known as characteristic features of lupus nephritis. However, both features are not pathognomonic for lupus nephritis. A kidney biopsy specimen showing full-house immunofluorescence pattern in the absence of autoantibodies and classical clinical features of Systemic Lupus Erythematosus (SLE) is now considered as nonlupus full-house nephropathy (FHN). Nonlupus FHN may be idiopathic or due to other disease processes known as secondary nonlupus FHN. Here, we report the case of a 36-year-old female who presented with nephrotic proteinuria with bland urine sediment. Additional analyses revealed normal serum antinuclear antibody (ANA), normal anti-double-stranded DNA (anti-dsDNA) antibodies, and normal serum C3 and C4 levels. A renal biopsy showed a normal-appearing glomerulus without any proliferation or capillary wall thickening and widespread glomerular immune deposits (full-house effect; IgA, IgG, IgM, C3, and C1Q) on direct immunofluorescence. Renal electron microscopy showed diffuse effacement of visceral epithelial cell foot processes and mesangial electron dense deposits. The patient was diagnosed as nonlupus FHN. There is a controversial role of steroids and other immunosuppressive drugs in the treatment of nonlupus FHN patients, but our case patient responded favourably to steroid therapy. The term nonlupus FHN can be used as an umbrella term for patients who do not satisfy the clinical and serological criteria of SLE.

Changes in the urinary content of uromodulin oligomeric forms in rats during development of urolithiasis

Введение. Изучение роли олигомерных форм уромодулина в развитии уролитиаза является важной фундаментальной и прикладной задачей. Несмотря на разнообразие моделей уролитиаза на лабораторных животных в настоящее время отсутствует информация относительно динамики концентрации и фракционного состава олигомерных форм уромодулина в моче животных на различных этапах развития патологического процесса. Цель - исследование динамики содержания олигомерных форм уромодулина в моче животных на фоне развития гипероксалатного уролитиаза индуцированного экзогенным введением 1% раствора этиленгликоля в качестве безальтернативного источника питья. Методика. Проводили общеклинический и биохимический анализ образцов крови и мочи на различных этапах развития патологического процесса. До начала моделирования патологии и на фоне экзогенного введения этиленгликоля был исследован осадок мочи. Оценка содержания олигомерных форм уромодулина в моче животных проводилась методом анализа треков наночастиц и динамического рассеяния света. Результаты. Показано, что на фоне развития патологии наблюдается уменьшение концентрации олигомерных форм уромодулина в моче, на начальных этапах развития патологии за счёт увеличения фракции крупных частиц (более 200 нм, олигомерная форма 28 МДа). При дальнейшем развитии патологического процесса на завершающем этапе наблюдается радикальное уменьшение концентрации частиц в моче (более чем в 2 раза). Заключение. Полученные данные показали относительно низкую корреляцию между длительностью моделирования патологии и тяжестью проявления уролитиаза (r-Пирсона = 0,49, p-value = 0,0003). Концентрация олигомеров уромодулина в моче животных уменьшается на фоне увеличения количества кристаллов в осадке мочи, что вероятно связанно с включением уромодулина в структуру кристаллов осадка. Studying uromodulin oligomeric forms in urolithiasis development is important fundamental and applied problem. Despite the variety of in vivo models of urolithiasis, there is currently no information about concentration dynamics and fractional composition of uromodulin oligomeric forms in urine for animals at various stages of pathological process developmen. The purpose We investigate dynamics uromodulin oligomeric forms in urine of animals against the background of development hyperoxalate urolithiasis induced by exogenous administration of 1% ethylene glycol solution as a non-alternative source of drinking. Methods. For urine samples at various stages of pathogenesis, general clinical and biochemical analysis were carried out, for urine samples before the start of pathology modeling and against the background of exogenous administration of ethylene glycol, urine sediment was examined. The study of urine sediment and content uromodulin oligomeric forms was carried out on 0th, 7th, 14th, 21st and 28th days of pathology modeling. Evaluation of the content of uromodulin oligomeric forms in urine of animals was carried out by nanoparticles track analysing and dynamic light scattering. Results. It is shown that against the background of the pathology development there is a decrease in the concentration of oligomeric forms of uromodulin in the urine, at the initial stages of pathology development due to an increase in the fraction of large particles (over 200 nm, oligomeric form 28 МDa). With further development of the pathological process at the final stage, there is a radical decrease in the concentration of particles in the urine (more than 2-fold). Conclusion. The obtained data showed a relatively low correlation between the duration of pathology modeling and the severity of urolithiasis manifestation (Pearson's r = 0.49, p-value = 0.0003). Concentration of uromodulin oligomers in animals urine decreases with an increase in the amount of crystals in urine sediment, which is probably associated with inclusion of uromodulin in structure of sediment crystals.

Urine Cellular DNA Point Mutation and Methylation as Potential Biomarkers for the Detection of Urothelial Carcinoma

BackgroundPreviously, our team identified a seven-gene mutation panel in urine sediment to discriminate UBC from benign urological diseases. In the present study, we aimed to validate the panel in an expanded and close to natural population cohort of hematuria. Also, we tried to optimize the panel by incorporating methylation biomarkers. We performed external validation to investigate the robustness and stability of the novel panel.MethodsPatients with urothelial carcinomas and controls were prospectively recruited in clinical trial ChiCTR2000029980. The mutation panel was validated in the expanded cohort(n=333) from Hunan multicenter. Several UBC-specific methylation biomarkers were identified by comprehensive analyses of a series of TCGA, GEO and an independent cohorts, and examined in the expanded cohort. Random Forest algorithm was used to construct an optimal panel. External validation of the optimal panel was carried out in Beijing single center cohort(n=89). NGS technique was used to analyze the DNA point mutations and MS-PCR for methylation.ResultsThe AUC, sensitivity and specificity of the mutation panel in expanded cohort were 0.81, 0.67 and 0.90, respectively. After screening, only cg16966315, cg17945976 and cg24720571 were left for further analysis. The optimal panel consisted of cg24720571 and 8 point mutations, including TERT.chr5_1295228 G_A (TERT 228), FGFR3.chr4_1803568 C_G (FGFR3 568), TERT.chr5_1295250 G_A (TERT 250), FGFR3.chr4_1806099 A_G (FGFR3 099), PIK3CA.chr3_178936091 G_A (PIK3CA 091), PIK3CA.chr3_178952085 A_G (PIK3CA 085), PIK3CA.chr3_178936082 G_A (PIK3CA 082), HRAS.chr11_533874 T_C (HRAS 874). The AUC, sensitivity and specificity of the optimal panel in training group were 0.89, 0.84 and 0.79, respectively, and in test group were 0.95, 0.91 and 0.95, respectively. In the external validation, the AUC, sensitivity and specificity were 0.98, 0.93 and 0.93, respectively.ConclusionsThe optimal panel was obviously superior to previous mutation panel and showed a highly specific and robust performance. The optimal panel may be used as a replaceable approach for early detection of UC.Trial registrationThis research was registered in Chinese Clinical Trial Registry(ChiCTR2000029980).

Bacterial Morphotypes as Important Trait for Uropathogenic E. coli Diagnostic; a Virulence-Phenotype-Phylogeny Study

Urinary tract infections (UTIs) belong to the most common pathologies in Mexico and are mainly caused by Uropathogenic Escherichia coli (UPEC). UPEC possesses a wide diversity of virulence factors that allow it to carry out its pathogenesis mechanism in the urinary tract (UT). The development of morphotypes in UT represents an important feature of UPEC because it is associated with complications in diagnosis of UTI. The aim of this study was to determine the presence of bacterial morphotypes, virulence genes, virulence phenotypes, antibiotic resistant, and phylogenetic groups in clinical isolates of UPEC obtained from women in Sonora, Mexico. Forty UPEC isolates were obtained, and urine morphotypes were observed in 65% of the urine samples from where E. coli was isolated. Phylogenetic group B2 was the most prevalent. The most frequent virulence genes were fimH (100%), fliCD (90%), and sfaD/focC (72%). Biofilm formation (100%) and motility (98%) were the most prevalent phenotypes. Clinical isolates showed high resistance to aminoglycosides and β-lactams antibiotics. These data suggest that the search for morphotypes in urine sediment must be incorporated in the urinalysis procedure and also that clinical isolates of UPEC in this study can cause upper, lower, and recurrent UTI.

Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study

Acute kidney injury (AKI) is an abrupt deterioration of renal function often caused by severe clinical disease such as sepsis, and patients require intensive care. Acute-phase parameters for systemic inflammation are well established and used in routine clinical diagnosis, but no such parameters are known for AKI and inflammation at the local site of tissue damage, namely the nephron. Therefore, we sought to investigate complement factors C3a/C3 in urine and urinary sediment cells. After the development of a C3a/C3-specific mouse monoclonal antibody (3F7E2), urine excretion from ICU sepsis patients was examined by dot blot and immunoblotting. This C3a/C3 ELISA and a C3a ELISA were used to obtain quantitative data over 24 hours for 6 consecutive days. Urine sediment cells were analyzed for topology of expression. Patients with severe infections (n = 85) showed peak levels of C3a/C3 on the second day of ICU treatment. The majority (n = 59) showed C3a/C3 levels above 20 μg/ml at least once in the first 6 days after admission. C3a was detectable on all 6 days. Peak C3a/C3 levels correlated negatively with peak C-reactive protein (CRP) levels. No relationship was found between peak C3a/C3 with peak leukocyte count, age, or AKI stage. Analysis of urine sediment cells identified C3a/C3-producing epithelial cells with reticular staining patterns and cells with large-granular staining. Opsonized bacteria were detected in patients with urinary tract infections. In critically ill sepsis patients with AKI, urinary C3a/C3 inversely correlated with serum CRP. Whether urinary C3a/C3 has a protective function through autophagy, as previously shown for cisplatin exposure, or is a by-product of sepsis caused by pathogenic stimuli to the kidney must remain open in this study. However, our data suggest that C3a/C3 may function as an inverse acute-phase parameter that originates in the kidney and is detectable in urine.

Case Report: Silicosis and IgA nephropathy, an exceptional association

A 57-year-old male who had been working in masonry for 33 years was hospitalized for renal function decline associated with exertional dyspnea. He presented with hypertension and limb edema. Urinalysis revealed an active urine sediment with glomerular proteinuria at 1.5 g/24h and the renal biopsy identified mesangial IgA Nephropathy. Chest tomography scans showed signs of silicosis. The patient received Angiotensin-Converting Enzyme Inhibitors with stable renal function. To our knowledge, the association of silicosis-IgA nephropathy has rarely been reported in the literature. This case highlights the effect of chronic exposure to silica dust and its association with both silica and renal disease.

Profile of Urine Sediments in Elderly People with Hypertension

Elderly was a person who reaches the age more than 60 years that susceptible by the aging, such as hypertension. Hypertension was one of the factor for kidney disease. Hypertension is a disease that has systolic blood preasure up to 140 mmHg and diastolic up to 90 mmHg. Find out how the description of urine sediment in older people with hypertension. Type of descriptive type,include data collection, processing and presentation of data. Samples were taken as many 25 people with criteria for elderly people affected by hypertension. Urine examination is carried out by the Malbin-Streinheimer painting method. The result showed 19 people (76%) had hematuria or the possibility of infection and 6 people (24%) did not have hematuria.from the examination also obtained a cylinder of 6 people, namely 4 people (16%) 1/Lpb and 1/Lpb 2 people (8%). This cylinder provides an overview of kidney abnormalities. Urine sediment examination in elderly people with hypertension gives an overview of renal hypertension with discovery of a cylinder accompanied by microscopic hematuri.

A Novel Propidium Monoazide-Based PCR Assay Can Measure Viable Uropathogenic E. coli in Vitro and in Vivo

Background: Polymerase chain reaction (PCR) is an important means by which to study the urine microbiome and is emerging as possible alternative to urine cultures to identify pathogens that cause urinary tract infection (UTI). However, PCR is limited by its inability to differentiate DNA originating from viable, metabolically active versus non-viable, inactive bacteria. This drawback has led to concerns that urobiome studies and PCR-based diagnosis of UTI are confounded by the presence of relic DNA from non-viable bacteria in urine. Propidium monoazide(PMA) dye can penetrate cells with compromised cell membranes and covalently bind to DNA, rendering it inaccessible to amplification by PCR. Although PMA has been shown to differentiate between non-viable and viable bacteria in various settings, its effectiveness in urine has not been previously studied. We sought to investigate the ability of PMA to differentiate between viable and non-viable bacteria in urine. Methods: Varying amounts of viable or non-viable uropathogenic E. coli(UTI89) or buffer control were titrated with mouse urine. The samples were centrifuged to collect urine sediment or not centrifuged. Urine samples were incubated with PMA and DNA cross-linked using blue LED light. DNA was isolated and uidA gene-specific PCR was performed. For in vivo studies, mice were inoculated with UTI89, followed by ciprofloxacin treatment or no treatment. After the completion of ciprofloxacin treatment, an aliquot of urine was plated on non-selective LB agar and another aliquot was treated with PMA and subjected to uidA-specific PCR. Results: PMAs efficiency in excluding DNA signal from non-viable bacteria was significantly higher in bacterial samples in phosphate-buffered saline (PBS, dCT=13.69) versus bacterial samples in unspun urine (dCT=1.58). This discrepancy was diminished by spinning down urine-based bacterial samples to collect sediment and resuspending it in PBS prior to PMA treatment. In 3 of 5 replicate groups of UTI89-infected mice, no bacteria grew in culture; however, there was PCR amplification of E. coli after PMA treatment in 2 of those groups. Conclusion: We have successfully developed PMA-based PCR methods for amplifying DNA from live bacteria in urine. Our results suggest that non-PMA bound DNA from live bacteria can be present in urine, even after antibiotic treatment. This indicates that viable but non-culturable E. coli can be present following treatment of UTI, and may explain why some patients have persistent symptoms but negative urine cultures following UTI treatment.