Marcadores de necrose tubular aguda e lesão inflamatória glomerular no sedimento urinária de pacientes com síndrome / Acute tubular necrosis markers and inflammatory glomerular injury urinary sediment syndrome patients

Necrose tubular aguda (NTA) é a causa mais frequente de lesão renal aguda (LRA) em pacientes hospitalizados. Em pacientes com síndrome nefrótica (SNO), a NTA mimetiza, por vezes, quadro de glomerulonefrite rapidamente progressiva e requer instituição precoce de imunossupressores. A análise do sedimento urinário é uma ferramenta não invasiva, de baixo custo e ampla disponibilidade. O achado de células epiteliais no sedimento urinário de pacientes com LRA foi associado ao diagnóstico de NTA. Entretanto, estudos em pacientes com SNO associada são escassos. Técnicas de diagnóstico utilizando sedimento urinário corado normalmente não são utilizadas nesses casos. Além do mais, o sedimento urinário é uma importante fonte de proteínas; estudos proteômicos do sedimento urinário revelaram importantes frações de proteínas não encontradas em sobrenadante, que pode ser usado como potencial biomarcador de LRA. Nosso objetivo é identificar alterações citológicas e protéicas no sedimento urinário que permitam o diagnóstico diferencial entre NTA ou lesão inflamatória-proliferativa glomerular (INF) em pacientes com SNO. Trata-se de um estudo de corte transversal, onde foram incluídos 32 pacientes: 5 pacientes normais (grupo controle), 10 com NTA, 9 sem NTA e 8 com glomerulonefrites exsudativas. As células do sedimento urinário foram contadas, citocentrifugadas, coradas em hematoxilina/eosina ou Papanicolaou e contadas diferencialmente como pequenas (<30μm de diâmetro), médias (30-48μm)...

Acute tubular necrosis (ATN) is the most frequent cause of acute kidney injury (AKI) in hospitalized patients. In patients with nephrotic syndrome (NS), acute tubular necrosis mimic, sometimes, rapidly progressive glomerulonephritis and requires premature institution of immunosuppressive treatment. The analysis of urinary sediment is a noninvasive tool, low cost and wide availability. The found of epithelial cells in the urinary sediment of patients with AKI was associated to ATN diagnosis. However, studies in patients with AKI in the set of NS are scarce. Diagnostics techniques using stained urinary sediment are not ordinarily used in these cases. Furthermore, urinary sediment is an important source of proteins; proteomic studies revealed important fractions of proteins not found in urinary supernatant that could be used as potential biomarkers for AKI. Our goal is identify cytological alterations and protein in urinary sediment which allow the differential diagnosis between ATN and inflammatory-proliferative glomerular lesion (INF) in patients with NS. This is a cross sectional study, in which 32 patients were included: 5 normal patients (control group), 10 with ATN, 9 without ATN and 8 with exudative glomerulonephritis. The cells of urinary sediment were counted, cytocentrifuged, stained of hematoxylin/eosin or Papanicolaou and differentially counted as small (<30μm of diameter), medium (30-48μm)...

Assessment of urinary endothelin-1 and nitric oxide levels and their relationship with clinical and pathologic types in primary glomerulonephritis

To determine the relationship between the urinary endothelin (ET-1), nitric oxide (NO) levels and the clinical, pathologic types of primary glomerulonephritis (GN) patients, urinary levels of ET-1 and NO were detected in 27 patients with biopsy-proven primary GN and 12 normal controls by radioimmunoassay and by copper-plated and cadmium column reduction assay, respectively. The results showed that urinary ET-1 levels in the patients with primary GN were significantly higher than in normal controls (p < 0.01), while the urinary ET-1 levels in patients with moderate mesangial proliferation GN were significantly higher than those in patients with mild mesangial proliferation GN (p < 0.05). Urinary ET-1 levels in patients whose clinical feature was nephrotic syndrome were found to be higher than in patients whose clinical feature was nephritic syndrome. However, urinary NO levels were to the contrary (p < 0.05). The ratio of ET-1/NO in primary GN patients was significantly higher than that in normal controls, and it positively correlated with the 24-hour urinary excretion of protein. These results suggest that urinary ET-1 levels are related to the proliferation of mesangial cells. The imbalance between ET-1 and NO may be related to the pathogenesis of primary GN and the occurrence of proteinuria.

Study of urinary excretion of leukotriene B4 and prostaglandin E2 in patients with glomerulonephritis and bilharziasis

Estimation of urinary excretion of prostaglandin E2 [PGE2] and leukatriene B4 [LTB4] was studied in chronic liver disease patients with and without chronic glomerulonephritis [GN]. 44 chronic liver disease patients [Schistosomal or non-schistosomal] were divided into two groups: group A [21 patients] associated with chronic glomerulonephritis; group B [23 patients] without detectable urinary abonrmality. 10 adults [group C] served as healthy controls. PGE2 and LTB4 were estimated in 24 hours urine by radioimmunoassay technique. Urinary PGE2 was significantly higher in liver disease patients associated with chronic glomerulonephritis [group A] than patients with liver disease only [group B]. The latter group showed a significant higher PGE2 than the normal controls. Increased urinary LTB4 excretion was found in chronic liver disease patients associated with chronic glomerulonephritis compared to nromal adults. While no detectable difference was found in LTB4 excretion between patients with liver disease [group B] compared to normal adults. We concluded that urinary PGE2 and LTB4 excretion increase with the development of G.N yet the explanation for this increase is postulated to be different. Increased manry PGE2 excretion is a translation to an endosgenous renal protective mechanism, while the increase in LTB4 excretion reflects the severity of the inflammatory process of the kidney

Transforming growth factor beta (TGF ß) activity in urine of patients with glomerulonephritis

Several lines of experimental evidence have shown that transforming growth factor ß (TGF ß) may play a major role in glomerular diseases, mediating the inflammatory response through glomerulosis. In the present study we evaluated TGF ß activity in occasional urine samples from 7 normal individuals and from 15 patients (10 with focal glomerular sclerosis and 5 with membranous glomerulonephritis) using a CCL-64 mink lung cell growth inhibition assay. Urinary TGF ß activity (reported in relation to urine creatinine concentration, Ucr, mean +/- SD) was higher in patients with focal glomerular sclerosis (x/- 17.32 +/- 15.75 / 10 µg Ucr) and patients with membranous glomerulonephritis (x/- = 17.78 +/- 11.53 / 10 µg Ucr) than in normal individuals (x/- = 0.8 +/- 0.44 / 10 µg Ucr). We also observed that TGF ß activity in urine from patients with focal glomerular...

Reduction of urine volume ameliorates adriamycin-induced nephropathy

1. Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. 2. The effect of urine volume on the progression of adriamycin-induced nephropathy was studied in 70 male Wistar rats (180-200 g) observed for 30 weeks and separated into 4 groups: healthy control group (HCG, N = 10) inoculated i.v. with 1 ml of saline, and nephrotic groups inoculated iv with a single dose of adriamycin of 3 mg/kg body weight. The nephrotic rats were separated into 3 groups (N = 20): nephrotic control group (NCG) receiving only adriamycin; dehydrated nephrotic group (DNG) water deprived for 36 h within each 48-h period, and furosemide nephrotic group (FNG) treated with 12 mg/dl furosemide, and 0.9 g/dl NaCl in the drinking water. 3. The 30-week survival rates of the DNG (100 per cent ) and HCG (100 per cent ) were significantly higher than those of the NCG (85 per cent ) and FNG (55 per cent ). 4. The proteinuria observed in the HCG (range, 7.38 +/- 0.7 to 13.6 +/- 1.27 mg/24 h) was significantly lower than that observed for all the nephrotic groups throughout the experiment. The DNG presented significantly less proteinuria (range, 42.71 +/- 6.83 to 140.10 +/- 19.22 mg/24 h) than the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) from week 10 on. There was no significant difference between the mean 24-h proteinuria of the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) and the FNG (range, 35.82 +/- 7.91 to 221.54 +/- 26.74). 5. The mean frequency of damaged glomeruli was 0.3 per cent +/- 0.3 for HCG, 42 per cent +/- 6 per cent for CNG, 40.8 per cent +/- 8 per cent for DNG, and 47 per cent +/- 14 per cent for FNG. The median value of the tubulointerstitial lesion, evaluated by a semiquantitative method, was 0 in HCG, 10 in CNG, 8.5 in DNG and 9.5 in FNG (P < 0.05 for all groups compared to HCG). 6. The data indicate that reduction of urine volume has a protective effect on adriamycin-induced nephropathy

Urine examination as a diagnostic aid in haematuria.

Dried smears of urinary sediments stained with leishman's stain were examined and compared in 30 selected patient with haematuria. In 12 patients with microscopic haematuria and glomerular lesions, red cells were dysmorphic showing variation in size and shape, and were hypochromic [dehaemoglobinized]. While in the 18 patients with nonglomerular causes of haematuria red cells were uniform in size and shape and using this technique which is simple non ivasive, inexpensive, we could suggest a possible source of bleeding in cases of haematuria

Nephritis blunts urinary kallikrein excretion and aggravates DOCA/NaCl hypertension in rats

1. Normal rats and passive Heymann membranous glomerulonephritic rats were chronically treated with DOCA/NaCl for 9 weeks. Normal and untreated nephritic rats were used as controls. Urinary kallikrein excretion (UKE), proteinuria and tail blood pressure (BP) were determined in awake rats. Glomuerular filtration rate (GFR), plasma renin activity (PRA), and plasma potassium (PK) concentration were measured at the end of the experiment. 2. Comparasion between basal and 9th-week measurements indicated that DOCA/NaCl administration significantly increased (P < 0.05) UKE (3.96 ñ 0.30 vs 7.60 ñ 1.51 U/24 h) and 118 ñ 2 vs 135 ñ 6 mmHg) in normal rats, whereas in nephritic DOCA/NaCl-treated rats, UKE was unaltered (3.80 ñ 0.50 vs 3.40 ñ 0.30 U/24 h) and BP increased to higher levels (117 ñ 2 vs 152 ñ 3 mmHg) than in the normal DOCA/NaCl group (P < 0.05). Passive Heymann nephritis alone did not affect UKE (3.56 ñ 0.40 vs 3.60 ñ 0.80 /24 h) or BP (124 ñ 2 vs 125 ñ 2 mmØg). At the end of the study, PK was decrease and PRA totally suppressed in both normal and nephritic DOCA/NaCl - treated rats. Proteinuria was more pronounced in nephritic DOCA/NaCl - treated rats (44.8 ñ 5.2 mg/day) than in control nephritic animals (15.1 ñ 2.4 mg/day) and GFR was increased equally in both DOCA/NaCl-treated groups. 4. The failure of nephritic rats respond to DOCA/NaCl by increasing UKE was not associated with any significant derangement of renal function or structure and may have been related to the aggravation of arterial hypertension in this group

Morfologia das hemácias no sedimento urinário: técnico de deteçäo de hematúria glomerular / Urinary erythrocyte morphology: method for detecting glomerular hematuria

Avalia-se o valor da morfologia das hemácias no sedimento urinário como método de detecçäo de hematúria glomerular. Estudou-se o sedimento urinário de 93 pacientes com hematúria (cuja etiologia foi glomerular em 46 e näo-glomerular em 47), mediante microscopia de contraste de fase. As hemácias foram contadas e, quanto à morfologia, classificadas em dismórficas ou isomórficas. Buscou-se verificar ainda a ocorrência de cilindros com hemácias e a presença de proteinúria. Houve associaçäo significativa (p < 0,05) entre a presença de dismorfismo e o diagnóstico clínico-laboratorial de hematúria glomerular. A máxima especificidade e o mais alto valor preditivo positivo (100%), mantendo-se suficiente sensibilidade (86,9%), ocorreram quando adotados como critério de dismorfismo, percentagens iguais ou superiores a 65% de hemácias dismórficas. Constatou-se a diferença significativa (p < 0,05) entre a presença de dismorfismo e de proteinúria como métodos de detecçäo de hematúria glomerular. Ficou demonstrado que a técnica da morfologia das hemácias de sedimento urinário constitui método eficaz para determinar a origem glomerular da hematúria, sendo superior à verificaçäo da proteinúria e obtendo-se melhor correçäo com o emprego de percentagens iguais ou superiores a 65% de hemácias dismórficas