Padrões morfológicos de lesão glomerular e correlação com achados clinicolaboratoriais de 43 crianças com síndrome nefrótica

OBJETIVOS: Avaliar a associação entre os parâmetros clinicolaboratoriais e alteração morfológica de biópsias renais em crianças com síndrome nefrótica. MÉTODOS: Os dados foram obtidos dos prontuários médicos de 43 crianças com síndrome nefrótica submetidas a biópsia renal. RESULTADOS: Vinte e oito pacientes eram do sexo masculino (65,1%), idades entre 1,4 a 12 anos (média de 4,7±3,2). Quarenta e dois pacientes (97,7%) apresentaram edema; 83,7%, oligúria e 32,5%, hipertensão arterial. A média de proteinúria foi 15,3g/1,73m²SC/dia e 55,8% apresentaram hematúria microscópica. As biópsias renais mostraram: glomerulonefrite proliferativa mesangial (GNPM) em 37,2%, glomeruloesclerose segmentar e focal (GESF) em 27,9%, alterações glomerulares mínimas (LM) em 25,6%, glomerulonefrite membranoproliferativa (GNMP) em 7% e glomerulonefrite membranosa (GNM) em 2,3%. Vinte e seis pacientes (60,5%) apresentaram resistência ao corticosteróide. Idade, sexo, hipertensão arterial, oligúria, uréia e creatinina séricas não mostraram diferenças estatísticas significativas entre os pacientes com GNPM, GESF e LM. Os pacientes com GNPM e GESF apresentaram maior freqüência de hematúria microscópica (p < 0,003 e p < 0,03; respectivamente). Os pacientes com GESF apresentaram maiores níveis de proteinúria (p < 0,01 versus LM e p < 0,05 versus GNPM). Os pacientes com LM apresentaram sensibilidade ao corticosteróide (p < 0,001 versus GESF e p = 0,047 versus GNPM). CONCLUSÕES: Sexo, idade, presença de hipertensão arterial ou oligúria e níveis séricos de uréia e creatinina não auxiliaram na diferenciação entre pacientes com GNPM, GESF e LM. Os pacientes com LM apresentaram sensibilidade a corticosteróides e menos probabilidade de apresentar hematúria microscópica. Pacientes com GESF apresentaram maiores níveis de proteinúria.

Glomerulonefrite lúpica: estudo da evolução a longo prazo

OBJETIVO: Estudar a apresentação clínica e a evolução de pacientes portadores de glomerulonefrite lúpica. CASUÍSTICA E MÉTODOS: Foram estudados 37 pacientes portadores de glomerulonefrite lúpica, atendidos pela Disciplina de Nefrologia - Faculdade de Medicina de Botucatu, com seguimento médio de 52,4 ± 13,3 meses. Os dados foram obtidos através do levantamento retrospectivo dos prontuários. RESULTADOS: A idade média foi de 26,05 ± 11,12 anos, com predomínio do sexo feminino (84%) sendo que a glomerulonefrite classe IV foi a mais freqüente (80%). No início do seguimento a média da creatinina sérica foi de 1,74 ± 1,15 mg/dl, e a da proteinúria de 24h foi de 2,62 ± 2.89 g. Cinqüenta e um porcento dos pacientes com creatinina sérica elevada apresentaram, durante o seguimento, diminuição desses valores. Dentre diferentes variáveis estudadas, à época da biopsia renal, (idade, sexo, proteinúria, presença de hipertensão arterial e creatinina sérica) a única que se associou com pior prognóstico foi a elevação da creatinina sérica. Remissão da síndrome nefrótica ocorreu em 65% das vezes. A sobrevida atuarial foi de 96%, 82%, 70% e 70% em 1, 5, 10 e 12 anos. Cinco pacientes desenvolveram insuficiência renal crônica terminal e sete morreram, sendo infecção a principal causa de óbito (57%) CONCLUSÃO: em pacientes com nefropatia lúpica, o aumento da creatinina sérica, à época da biópsia, se associou com o desenvolvimento de insuficiência renal crônica ao fim do seguimento e a principal causa de óbito foi processo infeccioso.

On an acute case of Chagas disease in a region under vector control in the state of São Paulo, Brazil

Desde a década de 1970 não se notificavam casos autóctones de doença de Chagas aguda em São Paulo. em março de 2006 a Vigilância Epidemiológica registrou óbito por doença de Chagas aguda, em Itaporanga, de paciente de seis anos de idade. Exame histopatológico post mortem realizado no Hospital das Clínicas da Faculdade de Medicina de Botucatu confirmou o diagnóstico. Consultamos prontuários de hospitais e entrevistamos profissionais de saúde envolvidos além de familiares do paciente. Descrevemos medidas adotadas in loco para identificar a via de transmissão, reservatórios e vetores. Discutimos as possíveis fontes de infecção. Na região não foram identificados outros casos humanos, vetores ou reservatórios vertebrados infectados por Trypanosoma cruzi. Salientamos a importância de manter a vigilância, mesmo em áreas onde a transmissão de doença de Chagas está interrompida e naquelas ainda infestadas por triatomíneos. Deve-se admitir a hipótese diagnóstica de doença de Chagas quando observados: edema palpebral (uni ou bilateral), insuficiência cardíaca, miocardite, pericardite, anasarca, quadros similares aos de síndrome nefrótica ou glomerulonefrite sem causas outras aparentes, em pacientes com dados epidemiológicos positivos. Encontro, mesmo em raras ocasiões, de triatomíneos na região ou ainda contato com alimento contaminável com formas infectantes de T. cruzi.

PRESSER MECHANISMS IN ADRIAMYCIN-INDUCED NEPHROPATHY WITH HYPERTENSION IN RATS

We explored the role of angiotensin II and vasopressin in the maintenance of blood pressure during the nephrotic syndrome of adriamycin-induced nephropathy in rats. All 91 rats treated with adriamycin developed chronic renal failure with nephrotic syndrome, which was more pronounced in the normotensive rats than the 35% who became hypertensive. Angiotensin II blockade with DuP 753 produced a significantly greater hypotensive response in both the adriamycin-hypertensive (-16+/-3 mmHg) and adriamycin-normotensive (-14+/-5 mmHg) groups than the saline-treated controls (-5+/-1 mm Hg, P<.05). Vasopressin blockade with either a V1V2 inhibitor or a selective V-1 inhibitor produced a hypotensive response in adriamycin-hypertensive rats only (by -16+/-4 and -17+/-2 mm Hg, respectively, P<.01), although the nonselective vasopressin inhibitor produced similar fluid loss and body weight reduction in all three groups. The data suggest that in adriamycin-induced nephropathy with nephrotic syndrome, angiotensin II contributes to blood pressure maintenance in both hypertensive and normotensive animals, whereas the presser action of vasopressin contributes to elevated blood pressure in hypertensive animals only.

Paulista registry of glomerulonephritis: 5-year data report

Background. The Paulista Registry of Glomerulopathies was created in May 1999 and comprises several centres of São Paulo, the most populous Brazilian State, that concentrates people from all regions of the country who look for health care.Methods. This report includes data from 2086 patients from Brazil submitted to renal biopsy due to the presumed diagnosis of glomerular diseases, registered prospectively since May 1999 until January 2005. Data were collected by the integrants of the 11 centres involved, utilizing a standardized questionnaire.Results. The mean age of the patients was 34.5 +/- 14.6 years. Primary glomerular diseases were more frequent in males (55.1%) than in females; on the other hand, secondary glomerular diseases were more frequent in females (71.8%). The most common clinical presentation was nephrotic syndrome and the frequency of hypertension, at this time, was 55.5%. There was a predominance of indication of biopsies in the third, fourth and fifth decades of life. The most common primary glomerular diseases were focal and segmental glomerulosclerosis (29.7%), followed by membranous nephropathy (20.7%), IgA nephropathy (17.8%), minimal change disease (9.1%), membranoproliferative glomerulonephritis (7%), crescentic glomerulonephritis (4.1%), advanced chronic glomerulopathy (4%), non-IgA mesangial glomerulonephritis (3.8%), diffuse proliferative glomerulonephritis (2.5%), focal segmental proliferative glomerulonephritis (1%) and others (0.3%). The most frequent secondary glomerular disease was lupus nephritis, corresponding to 66.2% of the cases, followed by post-infectious glomerulonephritis (12.5%), diabetic nephropathy (6.2%), diseases associated to paraproteinaemia (4.9%), hereditary diseases (4.6%), vasculitis (3.2%), malignancies (0.9.%), secondary focal segmental glomerulosclerosis (0.6%) and others (0.9%).Conclusion. Focal segmental glomerulosclerosis was the most frequent primary glomerular disease, followed by membranous nephropathy and IgA nephropathy. Lupus nephritis predominated over all the other secondary glomerular diseases.

Effects of cyclosporine on adriamycin induced nephropathy

The effect of cyclosporine on adriamycin nephropathy was studied over both short (6 weeks) and long (26 weeks) periods. In the short-term study, cyclosporine was introduced 2 weeks after nephritis induction and in the long-term study, 14 weeks after the first adriamycin injection. The animals with adriamycin nephropathy treated with cyclosporine, studied for 6 weeks, developed proteinuria with increased renal size and glomerular area. The nephrotic animals treated with cyclosporine showed less proteinuria than the nephrotic control animals. There were no differences in glomerular area, creatinine clearance or serum creatinine and kidney weight between the treated nephrotic group and the health control group. The nephrotic animals, studied for the longer period, developed intense proteinuria, decreased creatinine clearance, glomerular necrosis and sclerosis, severe tubulointerstitial nephritis, increased hydroxyproline concentration and tubulointerstitial area. No difference was observed between the nephrotic animals treated with cyclosporine and those not treated. In conclusion, Cyclosporine A reduced proteinuria, glomerular hypertrophy and kidney weight in rats with short-term nephropathy but had no effect on the established nephropathy.

Estudo comparativo das complicações terapêuticas no Lúpus Eritematoso Sistêmico e nas glomerulopatias idiopáticas.

PURPOSE: To evaluate the therapeutic complications due to the use of immunosupressors in patients with nephropathy. METHODS: 76 patients who had used steroids and cyclophosphamide were retrospectively studied. The cases were divided into three groups: G1= 15 patients with Systemic Lupus Erythematosus without renal lesion; G2= 33 patients with lupus nephritis and G3= 28 patients with nephrotic syndrome owing to idiopathic glomerulopathy. RESULTS: There were no differences related to time of follow up (G1= 42.4 +/- 51, G2= 52.3 +/- 51, G3= 41.8 +/- 47.8 months), total used dosage of steroids (G1= 20, G2= 28, G3= 16 grams) and time of drug use (G1= 20, G2= 26, G3= 14.5 months). About cyclophosphamide use, there was no difference in the percentage of patients who used it (13% in G1, 51% in G2, 28% in G3), but the patients from G1 received lower total dosage than those from G2 (p<0.05). Cushingoid appearance, epigastric distress, psychiatric disorders, diabetes mellitus and ocular alterations occurred in all the three groups, with no statistically significant differences. The infections complications, those considered more severe clinically, were more frequent in G2 (G1= 6%, G2= 15%, G3= 0% - p<0.05), the same occurring with the deaths (7% in G1, 30% in G2, 0% in G3 - p<0.05). CONCLUSION: In patients with lupus nephritis there were more infections complications owing to prolonged immunosuppresion what may indicate a severity marker of this type of lesion.

Systemic hypertension in patients with glomerulonephritis

Although systemic hypertension is very common in patients with glomerulonephritis there is a dispute if this alteration is consequence of the glomerulonephritis per se or is a consequence of the renal failure secondary to the glomerular lesion. With the aim to analyze the factors associated with systemic hypertension, 196 patients with different forms of nephritis were studied. The systemic arterial pressure was measured by standard sphygmomanometer, renal function was evaluated by the determination of the serum creatinine concentration or creatinine clearance. The diagnosis of the type of glomerulonephritis was made on the basis of an examination of kidney biopsy specimens. The prevalence of arterial hypertension among patients with glomerulonephritis was 62.7%. The hypertensive patients were older (hypertensive = 30.6 ± 12.8; normotensive = 25.4 ± 1.6 years; P = 0.03). The prevalence of arterial hypertension was lower in patients with minimal glomerular lesion (12.5%), though their ages were also lower (18.1 ± 3.6 and 29.1 ± 1.03 years; P = 0.03). Arterial hypertension did not correlate with the serum levels of creatinine and albumin; creatinine clearance and 24-h proteinuria. In conclusion: In the patients with glomerulonephritis, the presence of arterial hypertension was associated with a higher mean age whereas the intensity of proteinuria, the level of renal function or the type of glomerulonephritis was not different between the two groups.

The role of myofibroblasts and interstitial fibrosis in the progression of membranous nephropathy

Renal interstitial fibrosis has been observed in a large number of nephropathies and contributes to the progressive deterioration of renal function. Myofibroblasts have been implicated in the reparative process of tissue injury, including renal scarring secondary to glomerular diseases. We performed a retrospective study on 28 patients with biopsy-proven primary membranous nephropathy, to determine whether interstitial myofibroblasts and tubulointerstitial lesions correlated with renal function at follow-up. Tubulointerstitial pathology was evaluated by morphometric and semiquantitative methods. Interstitial myofibroblasts were counted; 24-hour urinary protein and serum creatinine at the time of diagnosis and at the end of follow-up were available for all the patients. There were 20 males and 8 females, age 2-67 years (mean 42.3±153), most of them with nephrotic syndrome (78.6%). The final renal function had deteriorated in 16 patients (57.1%) and in 5 patients (17.8%) reached end-stage. The renal outcome was correlated with histological changes. We found a positive correlation between the severity of tubulointerstitial damage and the deterioration of the final serum creatinine (r 2=0.185; p=0.016). Myofibroblasts did not predict impaired renal function at the final follow-up. The current data do not support previous suggestions that myofibroblasts are a useful a predictor of end-stage renal disease.

Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients

The risk for venous thromboembolism (VTE) in medical patients is high, but risk assessment is rarely performed because there is not yet a good method to identify candidates for prophylaxis. Purpose: To perform a systematic review about VTE risk factors (RFs) in hospitalized medical patients and generate recommendations (RECs) for prophylaxis that can be implemented into practice. Data sources: A multidisciplinary group of experts from 12 Brazilian Medical Societies searched MEDLINE, Cochrane, and LILACS. Study selection: Two experts independently classified the evidence for each RF by its scientific quality in a standardized manner. A risk-assessment algorithm was created based on the results of the review. Data synthesis: Several VTE RFs have enough evidence to support RECs for prophylaxis in hospitalized medical patients (eg, increasing age, heart failure, and stroke). Other factors are considered adjuncts of risk (eg, varices, obesity, and infections). According to the algorithm, hospitalized medical patients ≥40 years-old with decreased mobility, and ≥1 RFs should receive chemoprophylaxis with heparin, provided they don't have contraindications. High prophylactic doses of unfractionated heparin or low-molecular-weight-heparin must be administered and maintained for 6-14 days. Conclusions: A multidisciplinary group generated evidence-based RECs and an easy-to-use algorithm to facilitate VTE prophylaxis in medical patients. © 2007 Rocha et al, publisher and licensee Dove Medical Press Ltd.

Pressor mechanisms in adriamycin-induced nephropathy with hypertension in rats

We explored the role of angiotensin II and vasopressin in the maintenance of blood pressure during the nephrotic syndrome of adriamycin-induced nephropathy in rats. All 91 rats treated with adriamycin developed chronic renal failure with nephrotic syndrome, which was more pronounced in the normotensive rats than the 35% who became hypertensive. Angiotensin II blockade with DuP 753 produced a significantly greater hypotensive response in both the adriamycin-hypertensive (-16 +/- 3 mm Hg) and adriamycin-normotensive (-14 +/- 5 mm Hg) groups than the saline-treated controls (-5 +/- 1 mm Hg, P < .05). Vasopressin blockade with either a V1V2 inhibitor or a selective V1 inhibitor produced a hypotensive response in adriamycin-hypertensive rats only (by -16 +/- 4 and -17 +/- 2 mm Hg, respectively, P < .01), although the nonselective vasopressin inhibitor produced similar fluid loss and body weight reduction in all three groups. The data suggest that in adriamycin-induced nephropathy with nephrotic syndrome, angiotensin II contributes to blood pressure maintenance in both hypertensive and normotensive animals, whereas the pressor action of vasopressin contributes to elevated blood pressure in hypertensive animals only.

Proteinuria predicts relapse in adolescent and adult minimal change disease

OBJECTIVE: This study sought to outline the clinical and laboratory characteristics of minimal change disease in adolescents and adults and establish the clinical and laboratory characteristics of relapsing and non-relapsing patients. METHODS: We retrospectively evaluated patients with confirmed diagnoses of minimal change disease by renal biopsy from 1979 to 2009; the patients were aged >13 years and had minimum 1-year follow-ups. RESULTS: Sixty-three patients with a median age (at diagnosis) of 34 (23-49) years were studied, including 23 males and 40 females. At diagnosis, eight (12.7%) patients presented with microscopic hematuria, 17 (27%) with hypertension and 17 (27%) with acute kidney injury. After the initial treatment, 55 (87.3%) patients showed complete remission, six (9.5%) showed partial remission and two (3.1%) were nonresponders. Disease relapse was observed in 34 (54%) patients who were initial responders (n = 61). In a comparison between the relapsing patients (n = 34) and the non-relapsing patients (n = 27), only proteinuria at diagnosis showed any significant difference (8.8 (7.1-12.0) vs. 6.0 (3.6-7.3) g/day, respectively, p = 0.001). Proteinuria greater than 7 g/day at the initial screening was associated with relapsing disease. CONCLUSIONS: In conclusion, minimal change disease in adults may sometimes present concurrently with hematuria, hypertension, and acute kidney injury. The relapsing pattern in our patients was associated with basal proteinuria over 7 g/day.

Minimal change disease associated with type 1 and type 2 diabetes mellitus

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents. Arq Bras Endocrinol Metab. 2012;56(5):331-5

Invariant Natural Killer T Cell Agonist Modulates Experimental Focal and Segmental Glomerulosclerosis

A growing body of evidence demonstrates a correlation between Th2 cytokines and the development of focal and segmental glomerulosclerosis ( FSGS). Therefore, we hypothesized that GSL-1, a monoglycosylceramide from Sphingomonas ssp. with pro-Th1 activity on invariant Natural Killer T ( iNKT) lymphocytes, could counterbalance the Th2 profile and modulate glomerulosclerosis. Using an adriamycin( ADM)-based model of FSGS, we found that BALB/c mice presented albuminuria and glomerular degeneration in association with a Th2-like pro-fibrogenic profile; these mice also expressed a combination of inflammatory cytokines, such as IL-4, IL-1 alpha, IL-1 beta, IL-17, TNF-alpha, and chemokines, such as RANTES and eotaxin. In addition, we observed a decrease in the mRNA levels of GD3 synthase, the enzyme responsible for GD3 metabolism, a glycolipid associated with podocyte physiology. GSL-1 treatment inhibited ADM-induced renal dysfunction and preserved kidney architecture, a phenomenon associated with the induction of a Th1-like response, increased levels of GD3 synthase transcripts and inhibition of pro-fibrotic transcripts and inflammatory cytokines. TGF-beta analysis revealed increased levels of circulating protein and tissue transcripts in both ADM- and GSL-1-treated mice, suggesting that TGF-beta could be associated with both FSGS pathology and iNKT-mediated immunosuppression; therefore, we analyzed the kidney expression of phosphorylated SMAD2/3 and SMAD7 proteins, molecules associated with the deleterious and protective effects of TGF-beta, respectively. We found high levels of phosphoSMAD2/3 in ADM mice in contrast to the GSL-1 treated group in which SMAD7 expression increased. These data suggest that GSL-1 treatment modulates the downstream signaling of TGF-beta through a renoprotective pathway. Finally, GSL-1 treatment at day 4, a period when proteinuria was already established, was still able to improve renal function, preserve renal structure and inhibit fibrogenic transcripts. In conclusion, our work demonstrates that the iNKT agonist GSL-1 modulates the pathogenesis of ADM-induced glomerulosclerosis and may provide an alternative approach to disease management.

The polysaccharide fraction of Propionibacterium acnes modulates the development of experimental focal segmental glomerulosclerosis

The pathogenesis of focal segmental glomerulosclerosis (FSGS) appears to be associated with type-2 cytokines and podocyte dysfunction. In this study, we tested the hypothesis that immunization with the polysaccharide fraction of Propionibacterium acnes (PS), a pro-Th1 agonist, may subvert the type-2 profile and protect podocytes from adriamycin-induced glomerulosclerosis. Adriamycin injection resulted in albuminuria and increased serum creatinine in association with loss of glomerular podocin and podoplanin expression, which is consistent with podocyte dysfunction. Renal tissue analysis revealed the expression of transcripts for GATA3 and fibrogenic-related proteins, such as TGF-beta, tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase 9 (MMP9). In association with the expression of fibrogenic transcripts, we observed peri-glomerular expression of a-smooth muscle actin (alpha-SMA), indicating epithelial-to-mesenchymal transition, and increased expression of proliferating cell nuclear antigen (PCNA) in tubular cells, suggesting intense proliferative activity. Previous immunization with PS inhibited albuminuria and serum creatinine in association with the preservation of podocyte proteins and inhibition of fibrogenic transcripts and the expression of alpha-SMA and PCNA proteins. Tissue analysis also revealed that PS treatment induced expression of mRNA for GD3 synthase, which is a glycosiltransferase related to the synthesis of GD3, a ganglioside associated with podocyte physiology. In addition, PS treatment inhibited the influx of inflammatory CD8(pos) and CD11b(pos) cells to kidney tissue. Finally, PS treatment on day 4 post-ADM, a period when proteinuria was already established, was able to improve renal function. Thus, we demonstrate that the PS fraction of P. acnes can inhibit FSGS pathogenesis, suggesting that immunomodulation can represent an alternative approach for disease management. (C) 2011 Elsevier GmbH. All rights reserved.