MYH9 and APOL1 gene polymorphisms and the risk of CKD in patients with lupus nephritis from an admixture population.

MYH9 polymorphisms have been described to be associated with the risk of CKD in non-diabetic nephropathy, HIV nephropathy and FSGS. Predominating in black descendants, MHY9 genetic variants could partially explain the excess risk of CKD associated with African ancestry. However, recent data suggests that APOL1 gene co-segregate with MYH9, and could be the gene truly associated with CKD risk. In this study, we evaluated the role of MYH9 and APOL1 gene polymorphisms in the risk of CKD in Brazilian patients with lupus nephritis (LN). A retrospective analysis of 196 LN patients was done. MYH9 rs4821480, rs2032487, rs4821481 and rs3752462, APOL 1rs73885319, rs16996616, rs60910145, rs71785313, and APOL3 rs11089781 gene polymorphisms were determined. Genetic ancestry was ascertained both by autossomal ancestry and mitochondrial haplogroup. Primary outcome was defined as doubling of serum creatinine (DC) or end stage renal disease (ESRD). Sixty-two patients presented the PO. In our population, MYH9 and APOL1 were not in LD. None APOL polymorphism was associated with the PO, whereas rs3752462 MYH9 polymorphism showed a positive association (HR3.72, 95%CI 1.47-9.38, p = 0.005). When we analyzed the MYH9 E1 haplotype, the GCCT carriers (1 or 2 alelles present in 29.7% in the PO group vs. 18.5% in controls) showed a significant association to the risk of PO, even after adjustments for baseline estimated creatinine clearance and autossomal ancestry (HR 2.0, 95%CI 1.2-3.4, p = 0.01). Our results show that in our population MYH9, but not APOL1, gene polymorphisms confer an increased risk of CKD in LN patients, independently of race.

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.

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.

Antibodies to ribosomal P proteins in lupus nephritis: a surrogate marker for a better renal survival?

OBJECTIVE: To define if antibodies to ribosomal P proteins disclose a better lupus nephritis long-term survival. METHODS: Sixty consecutive SLE patients with biopsy-proven nephritis (2004 ISN/RPS) were evaluated for renal survival parameters. Inclusion criteria were at least one serum sample at: renal flares, biopsy, and last follow-up until 2008. Anti-P was detected by ELISA/immunoblot and anti-dsDNA by indirect immunofluorescence/ELISA. RESULTS: Eleven patients (18%) with anti-P+ (without anti-dsDNA) during renal flare were compared to 49 (82%) persistently negative for anti-P throughout the study. At the final follow-up post-biopsy (6.3±2.5 vs. 6.8±2.4 years, p=0.36), the comparison of anti-P+/anti-dsDNA- with anti-P- group revealed a trend to lower mean creatinine levels (0.9±0.3 vs. 2.3±2.1 mg/dl, p=0.07), lower frequency of dialysis (0% vs. 35%, p=0.025), and higher frequency of normal renal function (91% vs. 53%, p=0.037). The overall renal survival was significantly higher in anti-P+/anti-dsDNA- compared to anti-P- (11.0±4.5 vs. 9.2±4.5 years, p=0.033), anti-dsDNA+/anti-P- (vs. 8.7±4.7 years, p=0.017), and anti-P-/anti-dsDNA- (vs. 9.8±4.3 years, p=0.09) groups. CONCLUSION: Our data supports the notion that anti-P antibody in the absence of anti-dsDNA during nephritis flares is a valuable marker to predict a better long-term renal outcome in lupus patients.

Association of the MCP-1 -2518 A/G polymorphism and no association of its receptor CCR2 -64 V/I polymorphism with lupus nephritis.

OBJECTIVE: To evaluate whether the A/G polymorphism at position -2518 in the regulatory region of the monocyte chemoattractant protein-1 (MCP-1) or the V/I polymorphism at position -64 of the receptor, CCR2, are associated with lupus nephritis (LN) or any clinical characteristics of the disease or with renal survival in a patient population. METHODS: We selected 197 patients with lupus nephritis and 220 matched healthy controls for study. MCP-1 and CCR2 genotyping was performed by polymerase chain reaction. Clinical and laboratory data were compiled from patients' charts over followup that ranged from 6 months to 10 years. RESULTS: The G/G genotype of MCP-1 was more common in LN patients (p = 0.019), while the A allele was associated with healthy controls (p = 0.007) as was the V allele of CCR2 (p = 0.046) compared to LN patients. Clinical index measures [SLE Disease Activity Index (SLEDAI)], immunological markers, renal histology, renal function at enrollment, and renal survival were not influenced by these polymorphisms. A less aggressive renal disease, measured by renal SLEDAI index, was associated with the V allele of the CCR2 gene polymorphism. CONCLUSION: These findings support that MCP-1 -2518 G/G is associated with LN but there was no association of this genotype with renal function or renal survival. When studying CCR2 -64 V/I polymorphism we showed a positive association of the V allele with healthy controls but no association of the genotype with LN patients.

Male gender results in more severe lupus nephritis.

Gender may produce different characteristics in the manifestation of systemic lupus erythematosus (SLE). The present study investigated the influence of gender on clinical, laboratory, autoantibodies and histopathological classes of lupus nephritis (LN). As much as 81 patients diagnosed with SLE (ACR criteria) and active nephritis, who underwent renal biopsy between 1999 and 2004, and who had frozen serum samples and clinical data available from the time of biopsy, were selected for this study. The presence of anti-P and antichromatin antibodies was measured using ELISA, and anti-dsDNA was measured using indirect immunofluorescence. All of the renal biopsies were reviewed in a blinded manner by the same expert renal pathologist. The charts were extensively reviewed for demographic and renal features obtained at the time of the biopsy. Of the 81 patients (13.6%), 11 were male SLE patients. Both male and female lupus patients were of similar age and race, and had similar durations of lupus and renal disease. The female patients had more cutaneous (95.7 vs. 45.5%, P = 0.0001) and haematological (52.9 vs. 18.2%, P = 0.04) involvements than the male SLE patients. In addition, the articular data, central nervous system analyses, serositis findings and SLEDAI scores were similar in both experimental groups. Positivity for anti-dsDNA, anti-ribosomal P and antichromatin did not differ between the two groups, and both groups showed similarly low C3 or C4 serum levels. Our analysis indicated that no histopathological class of LN was predominant in both males and females. Interestingly, the serum creatinine levels were higher in the male SLE patients compared to the female SLE group (3.16 +/- 2.49 vs. 1.99 +/- 1.54 mg/dL, P = 0.03), with an increased frequency of high creatinine (81.8 vs. 47.1%, P = 0.04) as well as renal activity index (7.6 +/- 3.5 vs. 4.8 +/- 3.5, P = 0.02). In addition, whilst the mean levels of proteinuria, cylindruria and serum albumin were markedly altered, they were comparable between both lupus men and women. Moreover, the frequencies of dialysis, renal transplantation and death were similar between the two groups. These data suggest that male patients had a more severe LN compared to women diagnosed with this renal abnormality.

Perfil dos pacientes encaminhados à terapia renal substitutiva de umambulatório de nefrologia pertencente a um hospital terciário / Profile of patients with end-stage renal disease before starting renalreplacement therapy, derived from a tertiary nephrology center

ambulatório de nefrologia de um hospital terciário. Materiais e métodos: Foram analisados retrospectivamente dados epidemiológicos, clínicos elaboratoriais de 246 pacientes com DRC encaminhados para TRS entre janeiro de 2004 e janeiro de 2006. Resultados: 50,6% eram homens, com54,5±15,5 anos de idade e tempo médio de acompanhamento de 24,8+34,5 meses. As principais causas de DRC foram: diabetes (DM-32,9%), hipertensãoarterial (HAS-25,2%) e glomerulonefrite crônica (GNC-13%). Apenas 20,6% apresentavam fistula artério-venosa (FAV) funcionante. Apenas três pacientes(1,2%) foram encaminhados a programa de diálise peritoneal (DP). Os homens tiveram chance 2,3 vezes maior de ter FAV confeccionada em relação àsmulheres (p=0,012 IC 1,2-4,4). Nos pacientes com mais de 12 meses de acompanhamento, havia chance 4,6 vezes maior para a presença de FAV(p=<0,0001 e IC 2,1-10,0). A doença com maior prevalência de FAV confeccionada foi doença renal policística (31,8%) e a com menor, DM (13,4%). Ospacientes diabéticos apresentaram risco 2,3 vezes maior de ter tempo de seguimento ambulatorial inferior a 12 meses (p=0,0027 e IC 1,3-3,9) e risco de2,3 vezes maior de não ter FAV confeccionada (p=0,029 e IC 1,1-4,9). Conclusão: Os dados analisados assemelham-se à estatística norte-americana emrelação ao DM como causa principal de DRC. O baixo encaminhamento para DP sugere dificuldade do sistema para absorver pacientes nesta modalidadee/ou tendência preferencial de encaminhamento para hemodiálise. Dificuldades locais concernentes à confecção de FAV refletem-se na baixa prevalênciade acessos funcionantes por ocasião do encaminhamento (20,6%), principalmente quando o tempo de seguimento é inferior a 12 meses, o sexo é ofeminino e a doença de base é DM.

Objectives: to analyze the profile of chronic kidney disease (CKD) patients before starting renal replacement therapy (RRT), from a tertiary nephrologycenter. Materials and Methods: we analyzed retrospectively, epidemiologic, clinical and laboratory data from 246 CKD patients assigned to RRT, fromJanuary 2004 to January 2006. Results: In this study, 50.6% were male. The main etiologies of CKD were: diabetes (DM-32.9%), hypertension (HTN-25.2%), and chronic glomerulonephritis (CGN-13%). The median age and follow-up time were 54.5+15.5 years and 24.8+34.5 months, respectively. Only20.6% patients had a patent arteriovenous fistula (AVF). Only 3 patients were assigned to a peritoneal dialysis program (PDP). After analysis, men had 2.3times greater chance of AVF through vascular access, than women (p=0.012, CI 1.2-4.4). However, for those with more than 12 months of follow-up, ahigher probability (4.6 times) of AVF was detected (p<0.0001, CI 2.1-10.0). PKD patients had the best scores for AVF placements (31.8%) and patients withdiabetes revealed the worst scores (13.4%). CGN presented the longest ambulatory follow-up time before starting RRT, whereas obstructive nephropathypresented the smallest. There was no difference between gender distribution and creatinine clearance in patients with and without diabetes. However,diabetic patients were 2.3 times more prone to have a follow-up time less than 12 months (p=0.0027, CI 1.3-3.9) and 2.3 times less prone to have anaccessible AVF (p=0.029, CI 1.1-4.9). Conclusions: The analyzed data in this tertiary hospital are in tandem with the North-American statistics, which referto diabetes as the main cause of CKD. The low number of patients assigned to a PDP suggests that the structure and organization of peritoneal dialysisfacilities cannot meet the demand and also suggests a preference towards hemodialysis as the mode of choice for RRT...

Uso da internet como um ambiente para discussão de casos clínicos / The internet as an environment for discussing clinical cases

Criou-se um espaço na internet para a discussão de casos clínicos no website da Sociedade Brasileira de Nefrologia (http://www.sbn.org.br). O objetivo deste trabalho é apresentar o funcionamento deste espaço virtual e os aprimoramentos gerados após sua implantação, em setembro de 2001. Atualmente, 62 casos já foram divulgados e diagnosticados. Todos estão arquivados neste espaço para consulta sem cadastro prévio. A internet mostrou-se também um ambiente propício à discussão anatomoclínica, uma vez que permite a participação de profissionais de centros distantes e sem condição local para este tipo de atividade, tão importante para o contínuo aprendizado da Medicina.

An environment was built on the Internet for discussing clinical cases on the website of the Brazilian Society of Nephrology (http://www.sbn.org.br). The aim of this work is to present the operation of this system and the improvements made since its introduction in September 2001. Up to the present moment, 62 cases have been published and diagnosed. All of them are stored in the website for consultation without any previous registration. The Internet also proved to be a promising environment for clinical-pathological discussion for allowing the participation of professionals from distant centers and without local conditions for this kind of activity of great importance for continuing education in Medicine.

Antibodies to ribosomal P proteins: a potential serologic marker for lupus membranous glomerulonephritis.

OBJECTIVE: To evaluate the relevance of antibodies to ribosomal P proteins (anti-P antibodies) in discriminating histopathologic patterns of lupus nephritis. METHODS: The study group comprised 81 consecutive patients with systemic lupus erythematosus who underwent renal biopsy and for whom frozen serum was available at the time of biopsy. All biopsy specimens were reviewed in a blinded manner, according to the 2004 criteria of the International Society of Nephrology and the Renal Pathology Society. Anti-P antibodies were detected by enzyme-linked immunosorbent assay (ELISA)/immunoblot analysis, and anti-double-stranded DNA (anti-dsDNA) was detected by indirect immunofluorescence/ELISA. RESULTS: Anti-P antibodies were detected in 18 patients (22%). The demographic and clinical features of patients with and those without anti-P antibodies were similar. Remarkably, analyses of biopsy specimens revealed that the frequency of anti-P antibodies in patients with class V lupus nephritis was higher than the frequency among patients with other classes of renal disease (72% versus 28%; P = 0.005). Accordingly, anti-P antibody-positive patients had a higher mean (+/-SD) proteinuria level compared with anti-P antibody-negative patients (6.4 +/- 4.8 versus 4.7 +/- 3.9 gm/dl; P = 0.046). Renal function was preserved in 6 of 7 patients who had both isolated anti-P antibodies and class V lupus nephritis. In contrast, anti-dsDNA was associated with proliferative-class lupus nephritis (P = 0.050) and higher creatinine levels (P = 0.014). Furthermore, 7 of 9 patients with isolated anti-P antibodies had class V lupus nephritis, and, more importantly, 5 of these 7 patients (71%) displayed a pure membranous pattern. Conversely, a tendency toward the predominance of class V lupus nephritis (67%) with concomitant proliferative lesions was observed when anti-P antibody was associated with anti-dsDNA. CONCLUSION: Our data introduce anti-P antibody as a novel serologic marker for membranous lupus nephritis and support the notion that the presence of isolated anti-P antibodies may discriminate patients with pure class V lupus nephritis, whereas the simultaneous presence of anti-dsDNA antibodies suggests class V disease with concomitant proliferative lesions.

Polymorphism of the FcgammaRIIalpha IgG receptor in patients with lupus nephritis and glomerulopathy.

OBJECTIVE: FcgammaRIIalpha is a low affinity receptor that has 2 codominantly expressed alleles, R131 and H131, which differ in their ability to bind immunoglobulin G (IgG) subclasses. Cells expressing H131 bind more efficiently complexed IgG2 than those expressing the R131 variant. The FcgammaRIIalpha polymorphism has been shown to be associated with lupus nephritis. We evaluated the relevance of FcgammaRIIalpha gene polymorphism in the development of lupus immune complex mediated nephritis, as well as its clinical and histological characteristics, by comparing the genotype and allelic distribution of this receptor in lupus nephritis to ethnically matched Brazilian patients with primary glomerulonephritis. METHODS: Patients with lupus nephritis (n = 76) and patients with diagnosis of primary glomerulonephritis (n = 63) established by kidney biopsies were recruited. FcgammaRIIalpha genotyping was performed by polymerase chain reaction with allele-specific primers to distinguish between the 2 allelic forms (H131 and R131). RESULTS: We observed a skewed frequency of genotype FcgammaRIIalpha-R/R131 and the R131 allele in patients with lupus nephritis compared to primary glomerulopathies (p < 0.05), which disappeared when we compared this population with lupus nephritis only to the group with proliferative glomerulonephritis (IgA nephropathy, membranoproliferative glomerulonephritis, and mesangial proliferative glomerulonephritis). No association was found between genotype distribution and histological class of lupus nephritis or renal insufficiency available at the beginning and end of followup. We found an association of genotype FcgammaRIIalpha-R/R131 with higher antinuclear antigen titers and complement 3 consumption (p < 0.05). CONCLUSION: The skewed distribution of FcgammaRIIalpha genotypes with the predominance of homozygous R/R131 genotype observed in patients with lupus nephritis over nonproliferative idiopathic glomerulonephritis emphasizes its importance as a heritable risk factor for immune complex mediated renal injury in Brazilian patients with lupus.

Glomerulopatias em pacientes idosos: aspectos clínicos e histológicos / Glomerular diseases in the elderly: clinical and hystological features

Objetivo :As glomerulopatias têm sido diagnosticadas com mais freqüência em indivíduos idoso,o que tem motivado os estudos nesta faixa etária. Nesta série de casos, apresentamos os diagnósticos histológicos e clínicos mais comuns entre os pacientes idosos submetidos a biópsia renal no HC-FMUSP.Métodos :Foi avaliada retrospectivamente uma série de casos de 65 pacientes com 60 anos ou mais, submetidos a biópsia renal no HC-FMUSP, de 1989 a 1999, com suspeita clínica de glomerulopatia. Os dados demográficos e clínicos foram extraídos de revisão de prontuários. Proteinúria nefrática foi definida como proteinúria de 24 horas maior ou igual a 3,5 g e insuficiência renal como dosagem de creatinina sérica maior do que 1,4 mgldf. Os dados são descritos em freqüências simples e a comparação entre proporções foi realizada através do qui-quadrado. As médias de variáveis contínuas foram analisadas através do teste t de Student. O valor de p<0,05 foi considerado como limite para significância estatística. Resultados :Insuficiência renal foi diagnosticada em 69(por cento) (45/65) dos pacientes e em 6(por cento) (39165) havia proteinúria nefrática no momento da biópsia. A glomerulonefrite membranosa (18 por cento) foi a lesão mais encontrada no HC-FMUSP, seguida de amifoidose (14 por cento), doença de lesões mínimas (14por cento) e vasculite pauci-imune (11por cento). Nos pacientes com GP, a creatinina média no momento do exame foi 2,5±1,0 mg/di e a proteinúria 6,2±5,4 gl dia. Nos portadores de amiloidose, creatinina média foi 2,7±2,4 mg/di e a proteinúria 9,1 ± 4,6 g/dia. Nos pacientes com vasculite pauci-imune, a creatinina sérica inicial foi 4,8 ± 2,0 mgldl e a proteinúria 0,810 ± 0,26 ao dia. Estavam em programa de diálise no momento da biópsia 14 por cento dos pacientes e 34 por cento daqueles sem indicação de diálise evoluíram com perda de função renal. Conclusões: A glomerulonefrite membranosa foi a lesão mais encontrada, seguida de amiloidose, doença de lesões mínimas e vasculite pauci-imune. Nas glomerulopatias primárias e amiloidose, predominou quadro clínico nefrótico e nas vasculites, a perda de função renal. A maioria dos pacientes tinha acometimento renal em grau avançado, o que pode estar refletindo viés de seleção, por conduta conservadora na indicação de biópsias renais em pacientes idosos.

Consenso brasileiro para o tratamento do lúpus eritematoso sistêmico (LES) / Brazilian consensus for the treatment of systemic erythematous lupus

Objetivo: Elaborar recomendação baseada na melhor evidência científica para o tratamento das diversas manifestações do lúpus eritematoso sistêmico. Métodos: Oito reumatologistas que trabalham em serviços que atendem um grande número de pacientes com lúpus eritematoso sistêmico (LES), alguns com pesquisa e publicações científicas nesta área, foram convidados para participar do grupo de trabalho. Também foram convidados um nefrologista e uma dermatologista que atuam em grandes centros universitários, com grande experiência no atendimento de pacientes com LES. Todos se reuniram para discutir o tratamento das diferentes manifestações do LES. O grupo foi subdividido em quatro grupos, cada qual ficando responsável por buscar a melhor evidência para o tratamento de um ou mais comprometimentos do LES. A última edição de um clássico livro-texto sobre lúpus, Dubois's lupus erythematosus, editado por Wallace e Hahn, em 2001, foi utilizado como base da discussão e trabalhos publicados nos últimos cinco anos foram pesquisados no banco de dados do MEDLINE, em busca da melhor evidência para o tratamento de pacientes com LES. Resultados: Por ser uma doença não muito freqüente, com manifestações clínicas e laboratoriais bastante heterogêneas, infelizmente, a maioria dos trabalhos que avalia a eficácia dos diferentes esquemas terapêuticos não contempla grande casuística e nem são randômicos e controlados. Salientamos também que as manifestações, assim como a gravidade da doença pode variar em diferentes grupos populacionais, razão pela qual devemos avaliar com cuidado os estudos realizados em grupos populacionais distintos

Insuficiência renal aguda infiltrativa causada por doenças linfoproliferativas / Infiltrative acute kidney failure by lymphroproliferative diseases

Relatam-se três casos de insuficiência renal aguda causada por infiltraçäo de células tumorais em parênquima renal. Dois pacientes apresentaram linfoma nao-Hodkin e um paciente apresentou leucemia mielóide crônica em crise blástica. O diagnóstico foi realizado pelo aumento do tamanho renal à ultrassonografia abdominal e por biópsia renal percutânea que demonstrou infiltraçäo dos rins pela neoplasia, tendo sido confirmado pela melhora funcional após a instituiçäo de quimioterapia. Esta causa de insuficiência renal aguda deve ser lembrada em doenças linfoproliferativas, pois apresenta evoluçäo renal favorável desde que o diagnóstico e tratamento sejam estabelecidos em tempo hábil.