Classification of Acute Rejection Episodes in Kidney Transplantation: a Proposal Based on Factor Analysis.

INTRODUCTION: Kidney transplantation is considered the ideal treatment for end-stage renal disease. Acute rejection can influence graft survival. The aim of this study was to propose a classification system for acute rejection based on factor analysis. MATERIALS AND METHODS: Data were collected from kidney transplant recipients with acute rejection diagnosis based on standard histological variables, the presence of peritubular eosinophils, and immunolabeling for lysozyme and myeloperoxidase in kidney tissue. Factor analysis was employed for data reduction and generation of a new case classification, with orthogonal rotation as a strategy to simplify factors, and principal component analysis was used as an extraction method. RESULTS: Seventy-nine kidney biopsies were obtained from 74 patients. The total population was divided into humoral rejection (39.2%), cellular rejection (34.1%), and mixed acute rejection (26.7%). No significant differences were found between the three groups in clinical and biochemical variables. We extracted 4 factors using factor analysis. The 1st factor was characterized by the presence of capillaritis, plasma cells infiltration, tubulitis, and inflammation. The 2nd factor included positivity for lysozyme and myeloperoxidase, while the 3rd factor included the presence of eosinophils and glomerulitis. The 4th component consisted of the presence of C4d and endarteritis. The cases belonging to the 3rd factor showed the greatest increase in serum creatinine. The cases belonging to the 4th factor exhibited greater urinary excretion of proteins. CONCLUSIONS: This proposal of classification of acute rejection could contribute to evaluate the prognosis of kidney transplant recipients.

Avaliação sequencial da proteinúria, albuminúria e eletroforese de proteínas urinárias durante a evolução do diabetes mellitus em cães / Evaluation of proteinuria, albuminúria and electrophoresis of urine protein during the progression of diabetes mellitus in dogs

O Diabetes Mellitus (DM) desenvolve pela deficiência de insulina, caracterizada por hiperglicemia crônica. Complicações são freqüentes e incluem: catarata, retinopatia, infecções recorrentes e cetoacidose. A hiperglicemia crônica pode promover diversas complicações a longo prazo, como a nefropatia diabética (ND). Nos humanos diabéticos, a alteração renal é uma das complicações mais importantes, caracterizada pela lesão glomerular associada usualmente a hipertensão arterial sistêmica. Diversos mecanismos foram propostos tais como em decorrência da hiperglicemia crônica por lesão nos podócitos e lesão túbulointersticial. Contudo, nos cães, até o momento, existem poucos estudos que demonstram a relação entre DM e lesão renal. Perda de proteína urinária, principalmente albumina, é uma característica de doença glomerular. Portanto, para o diagnóstico de ND foram avaliados: razão proteína: creatinina urinária (RPC), razão albumina: creatinina urinária (RAC), microalbuminúria e eletroforese proteínas urinárias utilizando gel de poloacrilamida (SDS-PAGE). O objetivo deste estudo foi avaliar, de modo seqüencial, a proteinúria e a albuminúria durante a progressão do DM. Quatorze cães diabéticos (Grupo A= 10 cães; Grupo B=4 cães que evoluíram posteriormente com doença concomitante), média de 124 meses de idade, maioria fêmea, prevalente a raça Poodle, foram acompanhados por 6 a 28 meses. O acompanhamento foi realizado a cada 30 ou 60 dias. Todos os cães apresentaram bom controle glicêmico (glicemia em jejum com média de 253,05 mg/dL; frutosamina sérica com média de 560,53 µmol/L). Ademais, os cães estudados não apresentaram dislipidemia, hipertensão arterial (sistólica, média 127,28 mmHg), poliúria, polidpsia, polifagia e perda de peso. Em relação à proteinúria, o Grupo A apresentou RPC na faixa de normalidade (0,013 a 0,83), enquanto que no grupo B houve o aumento gradual da RPC ao longo do tempo (de 0,019 para 3,40), sendo que o cão que apresentou maior valor foi o que desenvolveu linfoma linfoblástico. Os cães do Grupo A não apresentaram microalbuminúria (RAC 60KDa e < 60KDa, respectivamente) encontravam-se normais. Concluindo, foi observado que os cães diabéticos do Grupo A não desenvolveram ND, e a proteinuria e microalbuminúria do Grupo B foi decorrente, provavelmente, das doenças concomitantes. Ademais, o controle glicêmico, o tempo de duração do DM, o controle da PA e dislipidemia podem ter colaborado na prevenção da ND nos cães

Diabetes Mellitus (DM) is caused by insulin deficiency, which results in chronic hyperglycemia. Complications are common and include: cataract, retinopathy, recurring infections and ketoacidosis. Chronic hyperglycemia may promote several complications along the disease, including diabetic nephropathy (DN). In humans with diabetics, renal damage is one of the most serious complications of diabetes mellitus, and usually associated to arterial hypertension. Several mechanisms were proposed such as due to chronic hyperglycemia, podocyte and tubulointersticial lesions. In dogs, however, there are a few studies that could demonstrated the relationship between diabetes mellitus and renal injury. Urine protein loss, mainly albumin, is characteristic in glomerular disease. Therefore, in order to investigate the diabetic nephropathy urinary protein-to-creatinine ratio (UPC), microalbuminuria (MA) and urinary albumin-to-creatinine ratio (UAC) and urinary protein electrophoresis in polyacrilamide gel were determinated. The aim of this study was to sequentially evaluate proteinuria and albuminuria during the progression of DM in dogs. Fourteen diabetic dogs (Group A = 10 dogs; Group B=4 dogs that lately developed concomitant disease), mean age of 124 months, most female, prevalent breed was Poodle, were followed for 6 to 28 months. Data were recorded every 30 to 60 days. All dogs had good glycemia control (mean of fasting glycemia was 253,05 mg/dL; mean of serum fructosamine was 560,53 µmol/L). Moreover, absence of dyslipidemia, arterial hypertension (mean 127,28 mmHg), polyuria, polydipsia, polyphagia and weight loss were not observed. In relation to proteinuria, Group A showed normal levels of UPC (0,013 and 0,83), while Group B had gradual increase of UPC over time (from 0,019 to 3,40), and the highest value was detected in a dogs that developed lymphoblastic lymphoma during the study. Dogs of Group A did not have microalbuminuria (UAC 60KDa and < 60 KDa, respectively). In conclusion, diabetic dogs of Group A did not develop diabetic nephropathy over time, and proteinuria and MA detected in Group B may be in consequence of concomitant diseases. Moreover, glycemic control, duration of DM, controlling of blood pressure and dyslipidemia may have refrain the development of diabetic nephropathy in dogs

Lowering the threshold for defining microalbuminuria: effects of a lifestyle-metformin intervention in obese "normoalbuminuric" non-diabetic subjects.

BACKGROUND: We investigated whether levels of albuminuria (urinary albumin excretion (UAE)) below those conventionally accepted as microalbuminuria (<30 mg/day) are sensitive to correction of obesity and obesity-related risk factors. METHODS: The effects of a 12-month lifestyle modification-metformin program were evaluated in otherwise healthy overweight/obese "normoalbuminuric" subjects: group I with UAE of <10 mg/day (n = 23) and group II with UAE of 10-29 mg/day (n = 18). RESULTS: The subjects of group II were older and heavier, and had higher blood pressure (BP) and lower high-density lipoprotein (HDL) levels, than those of group I. Creatinine clearances were also higher in group II (148 +/- 14 ml/min) than in group I (108 +/- 9 ml/min). Although the intervention induced comparable reductions in obesity, BP, lipids and insulin levels in both groups, UAE was significantly reduced in group II (9.1 +/- 1.8 mg/24 h; 60% reduction; P < 0.001), and non-significantly in group I (0.75 +/- 0.5 mg/day; 12% reduction; P > 0.1). Additionally, greater reduction in creatinine clearance was observed in subjects with higher UAE rates. After the intervention, both groups achieved similar UAE rates (5.7 +/- 0.9 and 5.2 +/- 1.0 mg/day; P > 0.10). Basal UAE was related to the subjects' creatinine clearance (r = 0.38; P = 0.04). For both groups together, intervention-induced changes in UAE rates were not significantly related to BP, age, or body weight. However, for group II subjects, BP and UAE reduction were positively associated (r = 0.44; P = 0.03). CONCLUSIONS: UAE of 10-29 mg/day (hyperalbuminuria), below the conventionally used limit to define microalbuminuria, is already associated with a more adverse cardiovascular risk profile, and is exquisitely sensitive to interventions that reduce obesity, BP, and insulin resistance.