Dietary interventions to contrast the onset and progression of diabetic nephropathy. a critical survey of new data

This article is a critical overview of recent contributions on the dietary corrections and the foods that have been claimed to delay or hinder the onset of diabetic nephropathy (DN) and its progression to end-stage renal disease. Innovative dietary and behavioral approaches to the prevention and therapy of DN appear the more captivating in consideration of the rather well established protocols for glucose and blood pressure control in use. In addition to restricted caloric intake to contrast obesity and the metabolic syndrome, adjustments in the patient's macronutrients intake, and in particular some degree of reduction in protein, have been long considered in the prevention of DN progression. More recently, the focus has shifted to the source of proteins and the content of glycotoxins in the diet as well as to the role of specific micronutrients. Few clinical trials have specifically addressed the role of those micronutrients associated with diet proteins that show the most protective effect against DN. Research on clinical outcome and mechanisms of action of such micronutrients appears the most promising in order to develop both effective intervention on nutritional education of the patient and selection of functional foods capable of contrasting the onset and progression of DN

Biological Pathways and Potential Targets for Prevention and Therapy of Chronic Allograft Nephropathy

Renal transplantation (RT) is the best option for patients with end-stage renal disease, but the half-life is limited to a decade due to progressive deterioration of renal function and transplant failure from chronic allograft nephropathy (CAN), which is the leading cause of transplant loss. Extensive research has been done to understand the pathogenesis, the biological pathways of fibrogenesis, and potential therapeutic targets for the prevention and treatment of CAN. Despite the advancements in the immunosuppressive agents and patient care, CAN continues to remain an unresolved problem in renal transplantation. The aim of this paper is to undertake a comprehensive review of the literature on the pathogenesis, biological pathways of RT fibrogenesis, and potential therapeutic targets for the prevention and therapy of CAN

Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice

Atypical hemolytic uremic syndrome (aHUS) is frequently associated in humans with loss-of-function mutations in complement-regulating proteins or gain-of-function mutations in complement-activating proteins. Thus, aHUS provides an archetypal complement-mediated disease with which to model new therapeutic strategies and treatments. Herein, we show that, when transferred to mice, an aHUS-associated gain-of-function change (D1115N) to the complement-activation protein C3 results in aHUS. Homozygous C3 p.D1115N (C3KI) mice developed spontaneous chronic thrombotic microangiopathy together with hematuria, thrombocytopenia, elevated creatinine, and evidence of hemolysis. Mice with active disease had reduced plasma C3 with C3 fragment and C9 deposition within the kidney. Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI mice from thrombotic microangiopathy and aHUS. Thus, our data provide in vivo modeling evidence that gain-of-function changes in complement C3 drive aHUS. They also show that long-term C5 deficiency is not accompanied by development of other renal complications (such as C3 glomerulopathy) despite sustained dysregulation of C3. Our results suggest that this preclinical model will allow testing of novel complement inhibitors with the aim of developing precisely targeted therapeutics that could have application in many complement-mediated diseases.</p

Glomerulopatia do Transplante: Análise Clínico-Patológica

Transplant glomerulopathy is a sign of chronic kidney allograft damage. It has a distinct morphology and is associated with poor allograft survival. We aimed to assess the prevalence and clinic-pathologic features of transplant glomerulopathy, as well as determine the functional and histological implications of its severity. We performed a single-centre retrospective observational study during an eight-year period. Kidney allograft biopsies were diagnosed and scored according to the Banff classification, coupled with immunofluorescence studies. The epidemiology, clinical presentation, outcomes (patient and graft survival) and anti-HLA alloantibodies were evaluated. Transplant glomerulopathy was diagnosed in 60 kidney transplant biopsies performed for clinical reasons in 49 patients with ABO compatible renal transplant and a negative T-cell complement dependent cytotoxicity crossmatch at transplantation. The estimated prevalence of transplant glomerulopathy was 7.4% and its cumulative prevalence increased over time. C4d staining in peritubular capillaries (27.6%) was lower than the frequency of anti-HLA antibodies (72.5%), the majority against both classes I and II. Transplant glomerulopathy was associated with both acute (mainly glomerulitis and peritubular capillaritis) and chronic histologic abnormalities. At diagnosis, 30% had mild, 23.3% moderate and 46.7% severe transplant glomerulopathy. The severity of transplant glomerulopathy was associated with the severity of interstitial fibrosis. Other histological features, as well as clinical manifestations and graft survival, were unrelated to transplant glomerulopathy severity

Differences in clinicopathologic variables between Borrelia C6 antigen seroreactive and Borrelia C6 seronegative glomerulopathy in dogs.

BackgroundRapidly progressive glomerulonephritis has been described in dogs that seroreact to Borrelia burgdorferi, but no studies have compared clinicopathologic differences in Lyme-seroreactive dogs with protein-losing nephropathy (PLN) versus dogs with Borrelia-seronegative PLN.Hypothesis/objectivesDogs with Borrelia C6 antigen-seroreactive PLN have distinct clinicopathologic findings when compared to dogs with Borrelia seronegative PLN.AnimalsForty dogs with PLN and Borrelia C6 antigen seroreactivity and 78 C6-seronegative temporally matched dogs with PLN.MethodsRetrospective prevalence case-control study. Clinical information was retrieved from records of dogs examined at the University of California, Davis, Veterinary Medical Teaching Hospital. Histopathologic findings in renal tissue procured by biopsy or necropsy of dogs with PLN were reviewed.ResultsRetrievers and retriever mixes were overrepresented in seroreactive dogs (P &lt; .001). Seroreactive dogs were more likely to have thrombocytopenia (P &lt; .001), azotemia (P = .002), hyperphosphatemia (P &lt; .001), anemia (P &lt; .001), and neutrophilia (P = .003). Hematuria, glucosuria, and pyuria despite negative urine culture were more likely in seroreactive dogs (all P ≤ .002). Histopathologic findings were consistent with immune-complex glomerulonephritis in 16 of 16 case dogs and 7 of 23 control dogs (P = 006). Prevalence of polyarthritis was not different between groups (P = .17).Conclusions and clinical importanceC6 seroreactivity in dogs with PLN is associated with a clinicopathologically distinct syndrome when compared with other types of PLN. Early recognition of this syndrome has the potential to improve outcomes through specific aggressive and early treatment

Cryoglobulinaemic vasculitis: classification and clinical and therapeutic aspects

Cryoglobulinaemia may cause cutaneous vasculitis and glomerulonephritis, potentially leading to end stage renal failure. An important proportion of cryoglobulinaemias are secondary to hepatitis C virus infection. Emerging antiviral treatment options offer a chance for causal therapy of these cases of cryoglobulinaemia. This review summarises the classification and clinical and therapeutic aspects of cryoglobulinaemic vasculitis and glomerulonephritis

Microalbuminuria as Predictor of Early Glomerular Injury in Children and Adolescents with Sickle Cell Anaemia at Muhimbili National Hospital Dar es Salaam, Tanzania 2012

Microalbuminuria (MA) is the earliest marker of various diseases affecting the renal system. Its relevance in children and adolescents with sickle cell anaemia (SCA), who are known to be prone to renal complications, has not been fully explored in our setting. Several studies have shown microalbuminuria to be prevalent among SCA children. It is now used extensively as a sensitive test of preclinical glomerular damage. Microalbuminuria in the early stages of sickle cell nephro¬pathy is a hallmark of future deterioration of renal function. It is important to detect this early with routine surveillance. Intervention at this stage may prevent or at least delay the end stage renal disease. To determine the prevalence of microalbuminuria and its clinical correlates in children and adolescents with SCA attending sickle cell clinic at Muhimbili National Hospital. This was a hospital based descriptive cross-sectional study. Children and adolescents aged 3 – 18 years attending sickle cell clinic were randomly selected. Urine sample of all eligible children and adolescent with SCA was screened for microalbuminuria by special Micral urine taste strips (Cliawaived Microlalbumin 2-1 Combo, USA),with sensitivity and specificity of 96.5% and 98.3 respectively. The resting blood pressure (BP) measurements, haemoglobin level, were obtained and clinical events associated with microalbuminuria were recorded. Data were analyzed using Statistical Package for Social Science (SPSS) version 17 statistical packages. Chi-square test was used for categorical variables, and student t test for independent sample means. Binary logistic regression was used to analyze potential effect modifiers of microalbuminuria. The study group was made up of 120 subjects aged 3 to 18 years (53% females). Microalbuminuria (MA) was found in 29/120 (24%). None of the clinical characteristics (painful crisis, blood transfusion, abnormal pressure) were significantly related with MA. Haemoglobin levels were significantly lower in subjects with MA than in those without MA (5.9±1.2 vs 7.4±1.0g/dL, respectively)p=0.001 . In multivariate logistic regression model of MA both Hb level and age remain in the final model as clinical correlates of MA. Higher Hb level showed a protective effect against MA (Odds ratio=0.55) p=0.001 while subjects with MA were more likely to have older age. (Odds ratio=1.7) p=0.001 MA is common among children and adolescents with SCA and directly related to age and inversely related to the haemoglobin levels. Urinary MA measurement is a simple and non-invasive screening biomarker which may be utilized as part of routine health care in children and adolescents with SCA. Screening for microalbuminuria seems prudent after age 6 to 7 years especially in those with severe anaemia. Longitudinal studies are essential to determine the significance of childhood microalbuminuria in the development of renal diseas