Rol de la hematuria dismórfica en las enfermedades gomerulares / Role of urinary dysmorphic red blood cells in glomerular disease

INTRODUCCIÓN: El sedimento de orina es una herramienta en la práctica clínica empleada desde hace muchos años para la evaluación de enfermedades renales. La detección de hematuria dismórfica es útil en el diagnóstico de enfermedades glomerulares. OBJETIVOS: Agrupar las hematurias dismórficas en los casos con presencia de acantocitos y los que no los presentan, y correlacionar estos dos grupos con los hallazgos histológicos de las biopsias renales. MATERIAL Y MÉTODOS: Estudio observacional, retrospectivo y analítico. Se incluyeron los sedimentos de orina de 276 pacientes. Se analizaron dos grupos de hematuria dismórfica: D1 (presencia de acantocitos) y D2 (sin acantocitos), y se correlacionó con los hallazgos histológicos de la biopsia renal (glomerulopatías proliferativas y no proliferativas). Se analizaron los diferentes elementos formes de la orina (cilindros hemáticos, leucocitarios, céreos, granulosos, grasos), la creatinina plasmática y la proteinuria de 24 hs en los dos grupos de glomerulopatías. Posteriormente se realizó una regresión logística para evaluar las variables independientes entre los hallazgos del sedimento de orina, con los correspondientes odds ratio (OR) e intervalos de confianza (IC 95%). RESULTADOS: Se contó con 172 muestras provenientes de mujeres (62.3%) y 104 de hombres (37,7%). La presencia de acantocitos (D1) en las enfermedades glomerulares proliferativas (GP) fue 17 veces más frecuente comparada con las no proliferativas (GNP) OR 17.7 IC 95% (9.6-32.5) p 0.001. La presencia de cilindros hemáticos es ocho veces más frecuente en las GP OR 8 IC 95% (3.1-20.9). Los pacientes con hematuria no acantocitica (D2) es 5 veces más frecuente en una GNP OR 5.2 IC (2.4-11.3) p 0,001. La presencia de cilindros grasos fue más frecuente en los pacientes con GNP a diferencia de los cilindros leucocitarios, cuya frecuencia fue mayor en la GP. CONCLUSIONES: La presencia de hematuria dismórfica no acantocitica (D2) se correlacionó en la histología renal con la presencia de glomerulopatías no proliferativas (GNP) en forma significativa, a diferencia de la hematuria acantocitica y cilindros hemáticos que se observaron en glomerulopatías proliferativas, por lo tanto se considera una herramienta útil para poder diferenciar clínicamente estos dos grupos, sin remplazar la biopsia renal para el diagnóstico preciso y el pronóstico

INTRODUCTION: The analysis of urine sediment is a tool that has been used for many years in clinical practice to evaluate kidney diseases. Detecting dysmorphic red blood cells (RBC's) in urine is useful for the diagnosis of glomerular diseases. OBJECTIVES: To divide the cases of glomerular hematuria into two groups, depending on the presence or absence of acanthocytes, and to compare this factor with the histological findings of renal biopsies. METHODS: In this observational, retrospective, analytical study, urine sediments of 276 patients were included. Two groups of subjects with glomerular hematuria were analyzed: D1 (presence of acanthocytes) and D2 (absence of acanthocytes). The results were compared with the renal biopsy histological findings, i.e. proliferative glomerulonephritis and non-proliferative glomerulonephritis, considered separately. The formed elements of the urine (red blood cell, white blood cell, waxy, granular and fatty casts), plasma creatinine concentration and 24-hour urinary protein were tested in the two groups. A logistic regression analysis was later performed to assess the independent variables among urine sediment findings, with the corresponding odds ratio (OR) and confidence intervals (CI 95%). RESULTS: The samples were collected from 172 women (62.3 %) and 104 men (37.7 %). The presence of acanthocytes (D1) was 17 times more frequent in proliferative glomerulonephritis (PGN) than in non-proliferative glomerulonephritis (NPGN) [OR 17.7, CI 95% (9.6-32.5), p 0.001]. The presence of red blood cell casts was 8 times more frequent in PGN [OR 8, CI 95% (3.1-20.9)]. Cases of hematuria with no acanthocytes (D2) were 5 times more frequent in NPGN [OR 5.2, CI (2.4-11.3), p 0.001]. Fatty casts appeared more frequently in patients with NPGN, whereas white blood cell casts were more common in PGN cases. CONCLUSIONS: Renal histological findings revealed a significant correlation between glomerular hematuria without acanthocytes (D2) and non-proliferative glomerulonephritis (NPGN), while the presence of acanthocytes and red blood cell casts was associated with proliferative glomerulonephritis (PGN). The existence of acanthocytes in urine constitutes a useful tool to make a clinical distinction between these two conditions, but it does not replace renal biopsy to establish an accurate diagnosis and prognosis

Erythrocyte and Biochemical Abnormalities as Diagnostic Markers in Dogs With Hemangiosarcoma Related Hemoabdomen.

OBJECTIVE: To investigate: 1) acanthocytosis and presence of acanthocytes in peritoneal fluid as a diagnostic marker for hemangiosarcoma (HSA) in dogs with non-traumatic hemoabdomen; and 2) the association between other erythrocyte, biochemical, and hematologic abnormalities as a mean of differentiating HSA from other disease. STUDY DESIGN: Prospective double-blinded cohort study. ANIMALS: Dogs (n = 40) with non-traumatic hemoabdomen. METHODS: Dogs diagnosed with hemoabdomen (January 2012 to May 2013) had cytologic evaluation of abdominal effusion and peripheral blood smears. Peripheral blood CBC, PT, and aPTT, as well as blood and effusion acanthocytes, keratocytes, schistocytes, lactate, glucose, PCV, and TP results were compared using the paired t-test or Fisher's exact test. Based on histologic confirmation of HSA, dogs were divided into 2 groups (HSA, non-HSA) and variables compared. RESULTS: There was no significant difference in erythrocyte morphology in abdominal effusion or peripheral blood between dogs with HSA or non-HSA related hemoabdomen. Platelet concentration and peripheral blood PCV were significantly lower in the HSA group. CONCLUSIONS: A reliable preoperative biochemical or cytologic test to differentiate between HSA and non-HSA related hemoabdomen was not identified.

Acanthocytosis and the c.680 A>G Mutation in the PANK2 Gene: A Study Enrolling a Cohort of PKAN Patients from the Dominican Republic.

Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). Pantothenate kinases catalyze the rate-limiting step of coenzyme A synthesis and Pank2 is the only pantothenate kinase isoform in humans that is localized to mitochondria. Acanthocytosis, the occurrence of spiculated erythrocytes, is observed in about 10% of the PKAN patients. Therefore PKAN is also classified together with other rare neurodegenerative diseases like Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS) into the Neuroacanthocytosis (NA) syndromes. It has not been investigated yet whether acanthocytosis in PKAN is associated with a specific subset of Pank2 mutations. In this study, we analyzed acanthocytosis of a cohort of 25 PKAN patients from the Dominican Republic that are homozygous for the c.680 A>G mutation in the PANK2 gene as compared to control donors that are heterozygous or wild-type with respect to this mutation. 3D modeling of this mutation indicated that the replacement of a tyrosine by a cysteine at position 227 in Pank2 disrupts a polar interaction within the A domain of the enzyme. Mean acanthocyte count was elevated in the cohort of patients, however, acanthocytosis varied among the patients with nearly half of them showing high (>20%) or elevated acanthocytosis and the rest showing mild (6-10%) or no (<6%) acanthocytosis. Heterozygous control donors revealed a tendency to mild acanthocytosis. Based on the insight that Pank2 is a normal constituent of red blood cells and de novo biosynthesis of coenzyme A is likely to take place in the erythrocyte cytosol we propose a hypothetical model that accounts for the variability in the occurrence of acanthocytic cells in PKAN.

[Clinical significance of new urine red blood cell parameter in different kinds of glomerulonephritis].

OBJECTIVE: To investigate the clinical value of new kinds of urinary erythrocyte morphology parameter in discriminating different pathology types of glomerulonephritis. METHODS: All of the 52 urine samples were from glomerulonephritis patients who had been diagnosed by renal biopsy results. The change of the percentage of acanthocytes, the size of RBC, the shape of RBC between the primary glomerulonephritis (39 cases) and secondary glomerulonephritis (13 cases) urine were detected by AVE-764 fully automatic urine cell analyzer. RESULTS: Acanthocytes could be found in both primary glomerulonephritis and secondary glomerulonephritis. Of the patients whose acanthocytes percentages above 10%, 94.1% had primary glomerulonephritis and 5.9% had secondary glomerulonephritis. The picture of size-shape phase were classified as strip-type, inverted triangle-type and hanging tail-type. 95.2% Strip-type cases were from primary glomerulonephritis patients. Triangle-typenormally cases were all from primary glomerulonephritis patients. Hanging tail-type cases were all from secondary glomerulonephritis. CONCLUSION: High acanthocytes percentage is most common in primary glomerulonephritis, going with the size and shape of RBC can be useful in the differential diagnosis of different pathology types of glomerulonephritis.

Poikilocytosis in rabbits: prevalence, type, and association with disease.

Rabbits (Oryctolagus cuniculus) are a popular companion animal, food animal, and animal model of human disease. Abnormal red cell shapes (poikilocytes) have been observed in rabbits, but their significance is unknown. The objective of this study was to investigate the prevalence and type of poikilocytosis in pet rabbits and its association with physiologic factors, clinical disease, and laboratory abnormalities. We retrospectively analyzed blood smears from 482 rabbits presented to the University of California-Davis Veterinary Medical Teaching Hospital from 1990 to 2010. Number and type of poikilocytes per 2000 red blood cells (RBCs) were counted and expressed as a percentage. Acanthocytes (>3% of RBCs) were found in 150/482 (31%) rabbits and echinocytes (>3% of RBCs) were found in 127/482 (27%) of rabbits, both healthy and diseased. Thirty-three of 482 (7%) rabbits had >30% acanthocytes and echinocytes combined. Mild to moderate (>0.5% of RBCs) fragmented red cells (schistocytes, microcytes, keratocytes, spherocytes) were found in 25/403 (6%) diseased and 0/79 (0%) healthy rabbits (P = 0.0240). Fragmentation and acanthocytosis were more severe in rabbits with inflammatory disease and malignant neoplasia compared with healthy rabbits (P<0.01). The % fragmented cells correlated with % polychromasia, RDW, and heterophil, monocyte, globulins, and fibrinogen concentrations (P<0.05). Echinocytosis was significantly associated with renal failure, azotemia, and acid-base/electrolyte abnormalities (P<0.05). Serum cholesterol concentration correlated significantly with % acanthocytes (P<0.0001), % echinocytes (P = 0.0069), and % fragmented cells (P = 0.0109), but correlations were weak (Spearman ρ <0.02). These findings provide important insights into underlying pathophysiologic mechanisms that appear to affect the prevalence and type of naturally-occurring poikilocytosis in rabbits. Our findings support the need to carefully document poikilocytes in research investigations and in clinical diagnosis and to determine their diagnostic and prognostic value.

Disease distribution in canine patients with acanthocytosis: 123 cases.

BACKGROUND: An acanthocyte is an abnormally shaped erythrocyte. In veterinary medicine, acanthocytes have historically been associated with canine hemangiosarcoma. In human medicine, acanthocytes are rarely observed with neoplastic disease and are more commonly associated with a variety of hereditary and acquired diseases. OBJECTIVES: The purpose of the study was to determine what disease processes are associated with the presence of acanthocytes in the peripheral blood of dogs. METHODS: Medical records for dogs presented to the Veterinary Teaching Hospital of Colorado State University during January 2004 through June 2008 with acanthocytes documented in their CBCs were retrospectively reviewed. RESULTS: A total of 123 dogs were included, 66 of which were diagnosed with neoplastic disease, most commonly hemangiosarcoma (n = 12), osteosarcoma (n = 11), and lymphoma (n = 11). The remaining 57 dogs had nonneoplastic disease, most commonly observed were gastrointestinal (n = 13), musculoskeletal (n = 8), renal (n = 8), and immune-mediated diseases (n = 7). No statistically significant difference was detected between percent acanthocytes present in dogs with neoplastic and nonneoplastic diseases. CONCLUSION: Acanthocytosis was observed with a variety of neoplastic and nonneoplastic diseases. While clearly commonly associated, the presence of acanthocytes in a blood smear should not be considered pathognomonic for hemangiosarcoma in dogs.

Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis.

XK is a putative transporter of unknown function that is ubiquitously expressed and linked through disulfide bonds to Kell protein, an endothelin-3 (ET-3)-converting enzyme. We generated three knockout (KO) mice that lacked either Xk, Kell or both proteins and characterized erythrocyte cation levels, transport and hematological parameters. Absence of Xk or Kell was accompanied by changes in erythrocyte K(+), Mg(2+), Na(+) and Ca(2+) transport that were associated with changes in mean cellular volume and corpuscular hemoglobin concentration mean. Baseline Ca(2+)-ATPase activity was undetected in erythrocytes from all three mouse types but was restored upon pre-incubation with ET-3. Consistent with these alterations in Ca(2+) handling, we observed increased Gardos channel activity in Kel and Xk KO mice. In addition Kel deletion was associated with increased Mg(2+) permeability while Xk deletion blocked Na/Mg exchanger activity. Our results provide evidence that cellular divalent cation regulation is functionally coupled to the Kell/XK system in erythrocytes and loss of this complex may contribute to acanthocytosis formation in McLeod syndrome.

Urine erythrocyte morphology in patients with microscopic haematuria caused by a glomerulopathy.

The evaluation of urinary erythrocyte morphology (UEM) has been proposed for patients with isolated microscopic haematuria (IMH) to early orientate the diagnosis towards a glomerular or a nonglomerular disease. However, to date, the role of this test in patients with IMH has very rarely been investigated. Sixteen patients (ten children, six adults) with persistent IMH classified as glomerular on the basis of repeated UEM evaluations (55 urine samples, two to eight per patient) were submitted to renal biopsy. This showed a glomerular disease in 14/16 patients (87.5%) (nine thin basement membrane disease; three Alport syndrome; two other), whereas in two patients, no abnormalities were found. Of four microscopic criteria investigated to define a IMH as glomerular, >80% dysmorphic erythrocytes were not found in any sample, >or=40% dysmorphic erythrocytes alone were seen in seven samples (12.7%), >or=5% acanthocytes alone in 15 samples (27.3%) and erythrocytic casts in six samples (10.9%). There was >or=40% dysmorphic erythrocytes associated with >or=5% acanthocytes in 25 samples (45.5%). Sensitivity and positive predictive values in diagnosing a glomerular haematuria were 59.2% and 90.6%, respectively, for >or=40% dysmorphic erythrocytes, 69.4% and 85% for >or=5% acanthocytes/G1 cells and 12.2% and 100% for erythrocytic casts. Our findings demonstrate that the evaluation of UEM is useful to identify patients with an IMH of glomerular origin.

The McLeod syndrome without acanthocytes.

A 45-year-old man developed chorea, behavioural changes, moderate amyotrophy and polyneuropathy. Hypertrophic cardiomyopathy and increased serum lactate dehydrogenase and creatine kinase (CK) were found. Acanthocytes were not detected. The absence of XK protein and faintly expressed Kell antigens on erythrocytes were found. Genetic test revealed a R133X mutation of the XK gene, confirming the McLeod syndrome. After 7 years he suddenly developed delirium followed by severe hypoglycaemia, hyperthermia, rhabdomyolysis, hepatic and renal failure. Malignant arrhythmia caused death.

Avaliação comparativa da sedimentoscopia urinária realizada pelo nefrologista e pelo profissional de análises clínicas em pacientes com glomerulopatias / Comparative assessment of urinary sediment done by the nephrologist and by the clinical analyst professional in patients with glomerulonephritis

Introdução: A sedimentoscopia urinária com microscópio munido com contraste de fase (MCF) deveria ser a primeira etapa na determinação da origemdas hematúrias. Objetivo: Avaliar discrepâncias nas descrições dos parâmetros urinários relacionados à origem das hematúrias, comparando as descrições do nefrologista (Nef) e do profissional de análises clínicas (PAC). Métodos: Urinas de pacientes com glomerulopatias (GP) confirmadas por biópsia renal foram analisadas sob MCF, por um Nef e um PAC, ambos sem conhecimento prévio da origem das amostras. Cilindros hemáticos, acantocitúria ou células G1 >5% e dismorfismo eritrocitário foram utilizados na localização glomerular das hematúrias. Resultados: Dos 28 pacientes, 13 pacientes (46,4%) apresentavam glomerulonefrites não proliferativas e 15 (53,6%) glomerulonefrites proliferativas. Comparativamente ao PAC, o Nef identificou maior número de hemácias (mediana/mL de urina, 80.000 vs 4.800, p=0,001), maior número de cilindros hemáticos (39,3% vs 0%, p=0,001), maior freqüência de acantocitúria ou células G1 >5% (35,7% vs. 7,14%, p=0,021) e de dismorfismo eritrocitário (96,2% vs 7,14%, p<0,001). As discrepâncias dos resultados permaneceram após a separação das glomerulopatias em proliferativas e não proliferativas. Conclusão: Os parâmetros urinários que caracterizam a origem da hematúria foram mais freqüentemente identificados pelo nefrologista e sugerem que a urinálise, pela sua simplicidade e grande valor informativo, deveria ser incluída obrigatoriamente nos programas de treinamento em nefrologia.

Introduction: In the assessment of hematuria, the first step should be the identification of the origin of the bleeding, which can be done easily by analyzing the urine under phase-contrast microscopy. Obective: To assess the discrepancy of reports of the urinary parameters utilized in the localization of the glomerular origin of hematuria, comparing reports by the nephrologists and by the clinical laboratory technologist. Methods: Urines of patients with biopsy proven glomerulonephritis were assessed under phase-contrast microscopy by a nephrologist and a clinical laboratory technologist, both without previous knowledge of the origin of the samples. Red blood cell (RBC) casts, urinary acanthocytes or G1 cells >5%, and erithrocyte dysmorphism were used tolocalize the glomerular bleeding. Results: Among 28 patients, 13 (46.4%) had non proliferative glomerulonephritis and 15 (53.6%) had proliferative glomerulonephritis. Relatively to the clinical laboratory technologist, the nephrologist identified more RBC (median of 80.000 vs 4.800, p= 0.001), more RBC casts (39.3% vs 0%, p=0.001), more urinary acanthocytes or G1 cells >5% (35.7% vs 7.14%, p=0.021) and more dysmorphic RBC (96.2% vs 7.14%,p<0.001). The discrepancies of the reports were maintained after the separation of the glomerulonephritis in proliferative and non proliferative. Conclusion: The urinary parameters used in characterization of the origin of the hematuria were more frequently identified by the nephrologist, and suggest that the urinalysis, a simple and very informative test, should be mandatory in programs of training in nephrology.

Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases.

The McLeod phenotype is derived from various forms of XK gene defects that result in the absence of XK protein, and is defined hematologically by the absence of Kx antigen, weakening of Kell system antigens, and red cell acanthocytosis. Individuals with the McLeod phenotype usually develop late-onset neuromuscular abnormalities known as the McLeod syndrome (MLS). MLS is an X-linked multi-system disorder caused by absence of XK alone, or when the disorder is caused by large deletions, it may be accompanied with Duchenne muscular dystrophy (DMD), chronic granulomatous disease (CYBB), retinitis pigmentosa (RPGR), and ornithine transcarbamylase deficiency (OTC). XK defects derived from a large deletion at the XK locus (Xp21.1) have not been characterized at the molecular level. In this study, the deletion breakpoints of two novel cases of McLeod phenotype with extensive deletions are reported. Case 1 has greater than 1.12 million base-pairs (mb) deletion around the XK locus with 7 genes affected. Case 2 has greater than 5.65 mb deletion from TCTE1L to DMD encompassing 20 genes. Phylogenetic analyses demonstrated that DMD, XK and CYBB have close paralogs, some of which may partially substitute for the functions of their counterparts. The loci around XK are highly conserved from fish to human; however, the disorders are probably specific to mammals, and may coincide with the translocation of the loci to the X chromosome after the speciation in birds. The non-synonymous to synonymous nucleotide substitution rate ratio (omega=dN/dS) in these genes was examined. CYBB and RPGR show evidence of positive selection, whereas DMD, XK and OTC are subject to selective constraint.

Dynamics of the structural and electrical characteristics of erythrocytes in men with metastatic adenocarcinoma of the prostate before and after plastic orchiectomy.

The changes of electrophoretic mobility of erythrocytes in the practically healthy men and in men with metastatic prostate cancer before and after castration were studied. The electrophoretic mobility of erythrocytes was investigated in laboratory conditions by Kharamanenko and Abramson micro methods. Experimental data were processed by means of standard variation statistics MINITAB (Basic statistic) p

[Hematuria and nephritic sediment]. / Marathonlauf, Nephritis oder Harnwegsinfekt? Wie Sie Blut im Urin rationell abklären.

Vigorous physical exercise is just as likely to be the cause of hematuria as are diseases of the efferent urinary tract, inflammatory renal disease or tumors. The microscopic search for dysmorphic erythrocytes (acanthocytes), casts or leukocytes in the sediment is a helpful technique for deciding the how to proceed with further diagnostic measures. Morphological changes in more than 17% of the erythrocytes are highly suggestive of a glomerular cause, Also, the presence of various casts points to kidney disease. The typical microscopic picture of interstitial nephritis is sterile leukocytosis. This may be of atheroembolic origin, medication-induced, or viral. In any case, the nephritic sediment should be clinically evaluated only in the context of further information such as the patient's age, comorbidities, or medication.

Acanthocytes in the urine: useful tool to differentiate diabetic nephropathy from glomerulonephritis?

OBJECTIVE: The presence of hematuria has been suggested to indicate nondiabetic nephropathy in diabetic patients with proteinuria. However, hematuria is frequently found in patients with biopsy-proven diabetic glomerulosclerosis without nondiabetic nephropathy. Urine microscopy allows discrimination of glomerular hematuria, which is defined as acanthocyturia (urinary excretion of acanthocytes, which are dysmorphic erythrocytes with vesicle-like protrusions), from nonglomerular hematuria. We hypothesized that acanthocyturia is an uncommon finding in diabetic nephropathy, which suggests the presence of a nondiabetic nephropathy in diabetic patients with proteinuria. RESEARCH DESIGN AND METHODS: Urine samples of patients with the clinical diagnosis of diabetic nephropathy (n = 68), of patients with biopsy-proven glomerulonephritis (n = 43), and of age-matched healthy control subjects (n = 20) were examined by phase-contrast microscopy for the presence of hematuria (>/=8 erythrocytes/ micro l) and acanthocyturia. Acanthocyturia of >/=5% (5 acanthocytes among 100 excreted erythrocytes) was classified as glomerular hematuria; acanthocyturia of 2-4% was classified as suspected glomerular hematuria. RESULTS: Hematuria was found in 62% of patients with the clinical diagnosis of diabetic nephropathy, in 84% of patients with glomerulonephritis, and in 20% of the healthy control subjects upon a single urine examination. In contrast, glomerular hematuria occurred in 4% of patients with diabetic nephropathy and in 40% of patients with glomerulonephritis (P < 0.001). CONCLUSIONS: In contrast to hematuria, acanthocyturia is uncommon in patients with the clinical diagnosis of diabetic nephropathy. In diabetic patients with proteinuria, the finding of acanthocyturia points to nondiabetic glomerulopathies, and renal biopsy should be considered.