Urinalysis - The Liquid Kidney Biopsy

Urine sediment examination is an important preliminary investigation for the nephrologist and helps him decide whether the patient has a proliferative or non-proliferative glomerular pathology. Recently, there is an increasing trend of using easier, non-specific dipstick method for urine examination leading to a decline in the importance of urine sediment examination. Here, we attempt to define guidelines for bio-chemical and microscopic parameters in order to develop a uniform and clinically relevant reporting system for urine sediment examination. Urine samples were reported as inactive or active sediment. A tiered system of reporting urine sediments was developed including inactive sediment, Inactive sediment with moderate/significant proteinuria, glomerular hematuria, and active sediment, active sediment with significant proteinuria / features of proliferative activity. The urine sediment was compared to kidney biopsies of these patients which were grouped into non proliferative and proliferative glomerulopathy. 795 paired samples of urine sediment and kidney biopsies were examined and compared. Patients of non-proliferative glomerulopathy (Minimal change disease, Focal segmental glomerulosclerosis, amyloid and membranous nephropathy) showed features of Inactive sediment. Patients with proliferative glomerulopathy (focal proliferative glomerulonephritis [GN], Diffuse proliferative GN, Membranoproliferative GN, Mesangio-proliferative GN and crescentic GN) predominantly showed active sediment, with increase in percentage of dysmorphic red blood cells and formed elements. The sensitivity of this urine reporting system was 82.0%, specificity 74.4% with p value <0.001. This system of reporting urine sediment is a sensitive and efficient method of predicting the severity of underlying kidney disease and need for performing renal biopsy.

Urine Sediment Examination in the Diagnosis and Management of Kidney Disease: Core Curriculum 2019

Urine sediment examination: A comparison of automated urinalysis systems and manual microscopy

Urine sediment examination is a time-tested and non-invasive diagnostic tool. Thisstudy investigated the characteristics of urine sediment and its association with severity and renal outcomes in diabetic nephropathy (DN) patients. A total of 201 biopsy-proven diabetic nephropathy patients (according to the pathological classification of diabetic nephropathyproposed by the Renal Pathology Society in 2010)who underwent manual urine sediment microscopic examination were included. We compared the clinicopathologicalcharacteristics of diabetic nephropathy patients with and without urinary renal tubular epithelial cells (RTECs) or renal tubular epithelial cell casts. The predictive value of urinary renal tubular epithelial cells or renal tubular epithelial cell casts for renal outcomes in diabetic nephropathy was analyzed. Fifty of 201 (24.9%) diabetic nephropathy patients had renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment. Diabetic nephropathy patients with renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment had a significantly higher level of proteinuria [6.0 (3.1, 9.7)vs.3.6 (1.8, 6.8) g/24h, p = 0.001], higher serum creatinine [227.9 (151.6, 338.1)vs.177.0 (104.4, 288.4) μmol/L, p = 0.016] and lower estimated glomerular filtration rate (eGFR) [25.8 (15.8, 44.8)vs.35.7 (19.9, 65.0) mL/min/1.73m2, p = 0.025] than those without.Cox regression analysis demonstrated that the presence of urinaryrenal tubular epithelial cells or renal tubular epithelial cell casts was independently associated with the development of end-stage kidney disease (ESKD) in diabetic nephropathy patients [HR 1.670, 95% CI (1.042, 2.676), p = 0.033]. Adding the presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts to the predictive model could improve the effectiveness of the model for predicting the risk of ESKD within one year after renal biopsy. The presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts was associated with more severe kidney injury and worse renal outcomes in patients with diabetic nephropathy, thus perhaps providing a noninvasive biomarker for predicting diabetic nephropathy.

The examination of urine sediment is a diagnostic test which is frequently neglected by nephrologists. With this review the authors wanted to demonstrate that it can provide useful and relevant information in a wide spectrum of clinical situations. The authors reviewed the main contributions dealing with urine sediment examination, published in international journals in the period from January 2002 to April 2003. After a section on methodological aspects, they described the importance of urine sediment examination in various diseases of the urinary tract. These included bladder B-lymphoma, systemic histoplasmosis, urate nephropathy, Fabry disease, myeloma cast nephropathy, giant cell arteritis, and lupus nephritis. The significance of 'decoy cells' in the urine as a marker of polyomavirus BK reactivation was also discussed, both in renal transplantation and other conditions such as solitary pancreas transplantation, chronic lymphatic leukaemia, and HIV infection. In the section devoted to urine sediment changes caused by drugs the authors dealt with leukocyturia induced by indinavir, and crystalluria, which can follow amoxycillin and acyclovir administration. Finally, they reported on the utility and limits of flow cytometry for the automated analysis of urine sediments. The review of the recent literature on urine sediment examination shows that this test has important clinical implications in a large spectrum of diseases. Therefore, it should be more widely used by nephrologists.

Introduction: Trichomoniasis is a curable sexually transmitted infection (STI) caused by a facultative anaerobic flagellate eukaryotic parasite called Trichomonas vaginalis, in its trophozoite form. It is a prevalent STI among women of reproductive age, causing vaginal discharge, increased risk of pelvic inflammatory disease and poor obstetric outcomes. According to the World Health Organization, in 2020, there were approximately 156 million new cases of the disease among people aged 15 to 49 years. One of the methods of visualizing T. vaginalis is through fresh microscopy, which is widely used to diagnose vaginitis. However, the parasite also infects the urinary tract and little has been studied about this site, although urinary sediment examination is a tool for its identification. Objective: To analyze the prevalence and characteristics associated with the diagnosis of T. vaginalis in the urinary sediment of women treated in the public sector in the municipality of Maranguape, Ceará. Methods: This is an observational, cross-sectional, quantitative clinical study carried out at the Municipal Hospital of Maranguape, Brazil, from February to December 2024, in which patients diagnosed with T. vaginalis infection were analyzed and their urine sediment exemined. Results: During the indicated period, 3,680 urine samples from patients of both genders and various age groups were analyzed. T. vaginalis was identified in nine patients (0.24%). Several trophozoites and their movements were visualized in all the positive urines. Most of the parasites were found between the leukocyte blocks, still with an apparent flagellum. They lost their strength of movement around 4 to 5 hours after collection. In the analysis of the urinary sediment, the positive samples had an acid pH (&lt;7), with a density varying between 1015 and 1030 g/mL, and the presence of protein in 44.4% of the samples. All the analyses showed some degree of leukocyte esterase, ranging from + (22.2%), ++ (33.3%) and +++ (44.4%), with leukocytes arranged in blocks on the slide. They also had bacteriuria associated with T. vaginalis, ranging from mild (88.8%) to moderate (11.1%). Hemoglobin was found in four of the nine positive samples (44.4%), and red blood cells were visualized in all of these samples, ranging from rare to numerous. It is believed that the visualization of trophozoites in urine slides is due to the fact that the microorganism grows and maintains itself in acidic media, with temperatures varying between 20° and 40°C, and can survive for a few hours in secretions, which would make it possible to diagnose it using urine sediment. Conclusion: The prevalence of T. vaginalis in urine tests was relatively low (0.24%). The parasite keeps moving for up to 5 hours. The characteristics of the urine sediment in these cases were low pH, bacteriuria and an increased number of leukocytes.

Urinary sediment is an important part of routine urine test, which plays an irreplaceable role in the diagnosis of diseases, monitoring of treatment effect, and prognosis judgment [1]. Through the results of urine dry chemistry and microscopic examination of urinary sediment, we inter-preted and analyzed the clinical significance of urinary casts in urinary sediment. In patients with new urinary system diseases abnormal urine results appear earlier than changes in serum renal function indicators, especially when the urine sediment shows typical casts, which can provide an important basis for clinical diagnosis. Clinical laboratory personnel should attach great importance to the morphological examination of urinary sediment and master the diagnostic significance of the formed components of urinary sediment for various diseases, so as to better assist clinical disease diagnosis.

The technique of supernatant removal in urine sediment examination using the Shih-Yung method can be done by aspirating and decanting. The aspirated technique is the recommended technique. The Central Laboratory Installation of Dr. M. Djamil Hospital, Padang used decanted supernatant removal technique. The variety of preanalytical procedures affect the results of urine sediment examination. This study aimed to analyze the agreement of erythrocyte, leukocyte, and non-hyaline cast sediment examination results using the Shih-Yung method in aspirated and decanted supernatant removal technique. This study was an analytical observational study with a cross-sectional design of 37 urine specimens that met the inclusion and exclusion criteria at the Central Laboratory Installation of Dr. M. Djamil Hospital, Padang from July to September 2020. Examination of erythrocyte, leukocyte, and non-hyaline cast sediment using Shih-Yung method with aspirated and decanted supernatant removal technique. Numeric data were analyzed using the Mann-Whitney U test and Cohen's Kappa test for the degree of agreement, p-value &lt; 0.05 was considered significant. The agreement test results for erythrocyte, leukocyte, and non-hyaline cast sediment in aspirated and decanted supernatant removal technique were (Kappa=0.88, p &lt; 0.05), (Kappa=0.83, p &lt; 0.05), and (Kappa=0.86, p &lt; 0.05), respectively. The degree of agreement test results for erythrocyte, leukocyte, and non-hyaline cast sediment using the Shih-Yung method in aspirated and decanted supernatant removal technique were almost perfect and statistically significant. The technique for supernatant removal in urine sediment examination using the Shih-Yung method can be done by decanting.

The presence of 'activated platelets' in the urinary sediments was studied by scanning electron microscopy (SEM) in patients with IgA nephropathy. The aim of the present study was to determine if the presence of activated platelets in the urinary sediments is correlated with glomerular injuries in patients with IgA nephropathy. Eleven patients with IgA nephropathy, 5 patients with thin basement membrane syndrome and 5 patients with membranous nephropathy were examined. The presence of platelets in glomeruli was also examined by immunofluorescence (IF). This study showed a correlation between the presence of activated platelets in the urinary sediments and the severity of glomerular injuries in patients with IgA nephropathy. The platelets were observed focally in glomeruli from such patients. It was suggested that the detection of activated platelets in the urinary sediments is useful in evaluating the degree of histopathological changes and/or prognosis of IgA nephropathy.

Urinary sediment is used to evaluate patients with possible urinary tract diseases. Currently, numerous protocols are applied to detect dysmorphic red blood cells (RBCs) and renal tubular epithelial cells (RTECs) in urinary sediment. However, distinct protocols are used by nephrologists and medical technologists for specimen concentration and observation, which leads to major discrepancies in the differential counts of formed elements such as dysmorphic RBCs and RTECs and might interfere with an accurate clinical diagnosis. To resolve these problems, we first tested a modified urinalysis protocol with an increased relative centrifuge force and concentration factor in 20 biopsy-confirmed glomerulonephritis patients with haematuria. We successfully improved the recovery ratio of dysmorphic RBCs in clinical specimens from 34.7% to 42.0% (P < 0.001). Furthermore, we confirmed the correlation between counts by the modified urinary protocol and Sysmex UF-1000i urinary flow cytometer (r ≥ 0.898, P < 0.001). A total of 28 types of isomorphic and dysmorphic RBCs were detected using a bright field microscope, with results comparable to those using a standard phase contrast microscope. Finally, we applied Sternheimer stain to enhance the contrast of RTECs in the urinary sediments. We concluded that this modified urinalysis protocol significantly enhanced the quality of urinalysis.

Liquid biopsy (LB) is a minimally invasive diagnostic tool which enables early detection, monitoring, and management of variety of diseases, including cancer, autoimmune, neurodegenerative, and infectious diseases. Analysis of molecular markers such as circulating tumor cells, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), extracellular vesicles, and other biomarkers in body fluids, offers insights into disease presence, progression, and treatment response. In cancer, LB allows for continuous tumor monitoring and overcomes the challenges of traditional tissue biopsies. In autoimmune diseases, LB can detect autoantibodies and immune complexes, offering a noninvasive way to monitor disease activity and therapeutic efficacy. In neurodegenerative conditions, biomarkers such as cfDNA and extracellular vesicles in cerebrospinal fluid help with early detection and tracking disease progression. For infectious diseases, LB can identify pathogen-derived DNA or RNA, enabling rapid diagnosis and monitoring of infections. Despite its promising potential, LB faces challenges such as lack of standardization, high sample-handling requirements, and high-cost detection techniques. Future developments, including artificial intelligence, may improve biomarker detection, test standardization, and large-scale clinical application.

Urine sediment examination is an integral part of urinalysis which is frequently overlooked as it can be time consuming and requires a functional microscope, a centrifuge and staff with both the time and expertise to perform the exam. Sediment examination allows the operator to identify crystals, casts, cells and bacteria in a urine sample. Failure to perform sediment examination promptly can lead to ageing artefacts which may negatively affect case management. Examination of the urine sediment should ideally be performed within 1–2 hours of urine collection.

Enzyme replacement therapy for Fabry disease: Morphologic and histochemical changes in the urinary sediments

The few available External Quality Assessment (EQA) programs on urinary sediment rarely include an evaluation of clinical cases. The present paper provides a descriptive analysis of clinical cases included in the Italian EQA program on urinary sediment. Ten cases were presented over a 5-year period (2007-2011). Each clinical case included a brief clinical history, some key laboratory data and four key urinary sediment particles obtained by phase contrast microscopy. The clinical diagnoses indicated by participants, chosen among four or five proposed, were evaluated only for those who had been able to correctly identify all four urinary sediment particles. The results of each survey were then evaluated, scored and commented on. The numbers of participants for the 10 surveys ranged from 268 to 325. Throughout surveys, only 63.9%±17.0% (range 39.6%-88.7%) of participants achieved access to clinical diagnosis. Of these, 90.2%±8.5% (range 73.7%-98.1%) were able to indicate the correct diagnosis. Our findings demonstrate that once the correct identification of urinary sediment particles is obtained, most participants are able to associate urinary findings with the respective clinical conditions, thus establishing the correct diagnosis.

Urinary sediments from 30 patients with endemic benign (epidemic) nephropathy (EBN) have been examined with phase contrast microscopy. Casts, often with an irregular outline, were found in 80% of the patients, most commonly in those showing the most advanced impairment of kidney function, as judged by the maximum concentration of serum creatinine registered during the acute phase of the disease. Conspicuously thin and long thread‐like objects of a kind not previously reported in the literature on the urinary sediment were seen in 40% of the patients; they possibly represented casts formed in the loop of Henle. Leukocyturia (&gt;5 leukocytes per visual field) was present in 20% of the cases. A number of cells sufficient for differential count was found in nearly all urine specimens examined: 15% granulocytes, 35% mononuclear leukocytes, 50% renal epithelial cells (REP) (mean values), a proportion of REP greater than that found at phase contrast microscopy of the urinary sediment in kidney diseases other than EBN. Microscopic hematuria of a few days' duration was found in 10% of the cases, a figure considerably smaller than previously reported. The findings seem to be almost pathognomonic for EBN and most of them were readily explained by the histopathologic changes found in percutaneous needle biopsy specimens of the kidney during the acute phase of the disease.