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Renal AND Proteinuria [keywords]
- Effects of oral carbonic adsorbent (AST-120) on kidney of early-stage chronic kidney disease rats. [JOURNAL ARTICLE]
- Ren Fail 2014 Nov 26.:1-6.
Abstract Aim: to investigate the therapeutic effects of oral carbonic adsorbent on rats with early-stage renal failure. Methods: The early-stage renal failure model was established with three-fourth subtotal nephrectomy Wistar rats. Four weeks after the subtotal nephrectomy, the rats were randomly divided into four groups: (1) adsorbent diet (AD) rats; (2) low protein diet (LPD) group; (3) low protein and AD rats; and (4) normal diet rats as control (ctrl) group. Sham operation group is set as well. The therapeutic effects of adsorbent were examined after 15 weeks treatment. Results: The level of 24 hours urinary protein excretion, serum creatinine (Scr), index of glomerulosclerosis (GSI) and tubulointerstitial fibrosis score (TIFS) of rats with adsorbent or LPD treatment are significantly lower than ctrl group rats. The combination of adsorbent and LPD lowered level of 24 hours urinary protein excretion, Scr, index of GSI and TIFS compared with LPD or adsorbent treatment alone. Conclusion: Both AST-120 and LPD treatment lowered the Scr and blood urea nitrogen level as well as ameliorated the proteinuria and glomerular and tubulointerstitial damage of rats with early stage renal failure. The combined treatment of oral carbonic adsorbent and LPD showed greater therapeutic effects.
- Pattern, clinical features and response to corticoids of glomerular diseases in a Brazilian population. An analytical cross-sectional study. [JOURNAL ARTICLE]
- Sao Paulo Med J 2014 Nov 28.:0.
Glomerular disease registries are increasing all around the world. The aim of this study was to evaluate the clinical characteristics and treatment response among patients with glomerular diseases followed up in a tertiary hospital in Brazil.Analytical cross-sectional study; tertiary-level public hospital.This study included patients with glomerular diseases followed up at a tertiary hospital in Fortaleza, northeastern Brazil. Clinical and laboratory data on each patient were registered. The response to specific treatment was evaluated after 3, 6 and 12 months.The study included 168 patients of mean age 37 ± 14 years. The most prevalent glomerular diseases were focal segmental glomerulosclerosis FSGS] (19.6%), minimal change disease MCD] (17.9%), membranous nephropathy MN] (16.7%) and lupus nephritis LN] (11.9%). The main clinical presentations were nephrotic proteinuria (67.3%) and renal insufficiency (17.9%). The mean proteinuria value decreased after the treatment began. Regarding 24-hour proteinuria on admission, there was no significant difference between patients with a good response and those with no response (7,448 ± 5,056 versus 6,448 ± 4,251 mg/24 h, P = 0.29). The glomerular disease with the highest remission rate was MCD (92%). Absence of interstitial fibrosis presented a strong correlation with remission (remission in patients without fibrosis = 83.4% versus 16.3% in those with fibrosis, P = 0.001).The present study found that the most frequent glomerular disease was FSGS, followed by MCD, MN and LN. The presence of interstitial fibrosis was a predictor of poor therapeutic response.
- Non-significant impact of proteinuria on renal function in Japanese patients with metastatic renal cell carcinoma treated with axitinib. [JOURNAL ARTICLE]
- Int J Clin Oncol 2014 Nov 26.
To investigate the impact of proteinuria on the renal function of patients with metastatic renal cell carcinoma (mRCC) who received axitinib, a tyrosine kinase inhibitor specifically targeting vascular endothelial growth factor receptors.This study included 65 consecutive Japanese patients who were diagnosed with mRCC and were subsequently treated with axitinib for at least 12 weeks. The association between the changes in the estimated glomerular filtration rate (eGFR) and proteinuria in these 65 patients was retrospectively assessed.Of the 65 patients, 41 (63.1 %) were judged to be positive for proteinuria. There were no significant differences between the eGFR value before the introduction of axitinib and that at the last clinic visit in either group with or without proteinuria. Furthermore, no significant correlation was noted between the changes in eGFR and the urine protein to creatinine ratio in the group positive for proteinuria, and there was no significant effect of the duration of treatment with axitinib on the changes in eGFR in the proteinuria group. Of several factors examined, univariate analysis identified age, eGFR prior to the introduction of axitinib, and timing of axitinib introduction, but not the presence of proteinuria, as predictors of a decrease in eGFR of >10 %; however, only age appeared to be independently associated with a decrease in eGFR of >10 %.These findings suggest that treatment with axitinib may not have a significant adverse impact on the renal function in patients with mRCC, irrespective of the presence of proteinuria.
- Dietary Restriction and Exercise for Diabetic Patients with Chronic Kidney Disease: A Systematic Review. [JOURNAL ARTICLE]
- PLoS One 2014; 9(11):e113667.
BackgroundObesity and sedentary lifestyle are major health problems and key features to develop cardiovascular disease. Data on the effects of lifestyle interventions in diabetics with chronic kidney disease (CKD) have been conflicting. Study DesignSystematic review. PopulationDiabetes patients with CKD stage 3 to 5. Search Strategy and SourcesMedline, Embase and Central were searched to identify papers. InterventionEffect of a negative energy balance on hard outcomes in diabetics with CKD. OutcomesDeath, cardiovascular events, glycaemic control, kidney function, metabolic parameters and body composition. ResultsWe retained 11 studies. There are insufficient data to evaluate the effect on mortality to promote negative energy balance. None of the studies reported a difference in incidence of Major Adverse Cardiovascular Events. Reduction of energy intake does not alter creatinine clearance but significantly reduces proteinuria (mean difference from -0.66 to -1.77 g/24 h). Interventions with combined exercise and diet resulted in a slower decline of eGFR (-9.2 vs. -20.7 mL/min over two year observation; p<0.001). Aerobic and resistance exercise reduced HbA1c (-0.51 (-0.87 to -0.14); p = 0.007 and -0.38 (-0.72 to -0.22); p = 0.038, respectively). Exercise interventions improve the overall functional status and quality of life in this subgroup. Aerobic exercise reduces BMI (-0.74% (-1.29 to -0.18); p = 0.009) and body weight (-2.2 kg (-3.9 to -0.6); p = 0.008). Resistance exercise reduces trunk fat mass (-0,7±0,1 vs. +0,8 kg ±0,1 kg; p = 0,001-0,005). In none of the studies did the intervention cause an increase in adverse events. LimitationsAll studies used a different intervention type and mixed patient groups. ConclusionsThere is insufficient evidence to evaluate the effect of negative energy balance interventions on mortality in diabetic patients with advanced CKD. Overall, these interventions have beneficial effects on glycaemic control, BMI and body composition, functional status and quality of life, and no harmful effects were observed.
- Endogenous female sex hormones delay the development of renal dysfunction in apolipoprotein E-deficient mice. [JOURNAL ARTICLE]
- Lipids Health Dis 2014 Nov 25; 13(1):176.
Hypercholesterolemia is a well-established risk factor for the development of kidney injury. Considering that female sex hormones may play a preventative role in both cardiovascular and renal diseases, the aim of the present study was to evaluate the effects of female sex hormones on hypercholesterolemia-induced renal dysfunction.Apolipoprotein E-deficient (ApoE) and C57 control female mice underwent an ovariectomy (OVX) or sham surgery and after 2 months, creatinine clearance, uremia and proteinuria were determined. Renal oxidative stress and lipid deposition were also quantified. Values are presented as mean +/- SEM. Statistical analyses were performed using Two-way ANOVA followed by Tukey's post hoc test.Creatinine clearance (muL/min) was similar between C57 (171 +/- 17) and ApoE (140 +/- 26) mice underwent sham surgery. OVX resulted in a reduced glomerular filtration rate in both C57 (112 +/- 8, ~ - 35%, p < 0.05) and ApoE (61 +/- 10, ~ - 56%, p < 0.05) animals. Plasma levels of urea (mg/dL) were higher in both ApoE groups (Sham: 73 +/- 7; OVX: 73 +/- 8, p < 0.05) when compared to C57 animals (Sham: 49 +/- 3; OVX: 60 +/- 4), with no changes among ovariectomized groups. Proteinuria levels (mg/24 h) were similar between C57 (Sham: 25.1 +/- 5.7; OVX: 33.7 +/- 4.7) and ApoE sham animals (26.4 +/- 3.5), however, 24-h urine protein excretion was augmented in ApoE OVX animals (49.6 +/- 5.8, p < 0.05). Histological kidney analysis demonstrated that the absence of female sex hormones resulted in increased oxidative stress, which was more severe in ApoE mice (C57 Sham: 9.2 +/- 0.4; C57 OVX: 22.9 +/- 1.0; ApoE Sham: 13.9 +/- 0.7; ApoE OVX: 34.0 +/- 1.4 au x 103, p < 0.05). As expected, ApoE mice presented higher lipid deposition, which was not affected by OVX (C57 Sham: 0 +/- 0; C57 OVX: 0 +/- 0; ApoE Sham: 6.8 +/- 1.6; ApoE OVX: 5.2 +/- 0.8% x 10-2, p < 0.05). Ovariectomy resulted in a similar reduction in ER-alpha protein expression in the renal cortex (C57: 0.78 +/- 0.04; ApoE: 0.81 +/- 0.04 au, p < 0.05) when compared to sham animals (C57:1.00 +/- 0.04; ApoE: 1.03 +/- 0.03 au).Taken together these data indicate that female sex hormones may delay hypercholesterolemia-induced renal dysfunction and emphasizes the importance of plasma cholesterol control in post-menopausal women.
- Drug-Induced Reduction in Albuminuria Is Associated with Subsequent Renoprotection: A Meta-Analysis. [JOURNAL ARTICLE]
- J Am Soc Nephrol 2014 Nov 24.
Albuminuria has been proposed as a surrogate end point in randomized clinical trials of renal disease progression. Most evidence comes from observational analyses showing that treatment-induced short-term changes in albuminuria correlate with risk change for ESRD. However, such studies are prone to selection bias and residual confounding. To minimize this bias, we performed a meta-analysis of clinical trials to correlate the placebo-corrected drug effect on albuminuria and ESRD to more reliably delineate the association between changes in albuminuria and ESRD. MEDLINE and EMBASE were searched for clinical trials reported between 1950 and April 2014. Included trials had a mean follow-up of ≥1000 patient-years, reported ESRD outcomes, and measured albuminuria at baseline and during follow-up. Twenty-one clinical trials involving 78,342 patients and 4183 ESRD events were included. Median time to first albuminuria measurement was 6 months. Fourteen trials tested the effect of renin-angiotensin-aldosterone-system inhibitors and seven trials tested other interventions. We observed variability across trials in the treatment effect on albuminuria (range, -1.3% to -32.1%) and ESRD (range, -55% to +35% risk change). Meta-regression analysis revealed that the placebo-adjusted treatment effect on albuminuria significantly correlated with the treatment effect on ESRD: for each 30% reduction in albuminuria, the risk of ESRD decreased by 23.7% (95% confidence interval, 11.4% to 34.2%; P=0.001). The association was consistent regardless of drug class (P=0.73) or other patient or trial characteristics. These findings suggest albuminuria may be a valid substitute for ESRD in many circumstances, even taking into account possible other drug-specific effects that may alter renal outcomes.
- Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease. [JOURNAL ARTICLE]
- J Am Soc Nephrol 2014 Nov 24.
Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN.
- Kidney disease among children in sub-Saharan Africa: systematic review. [REVIEW]
- Pediatr Res 2014 Nov 24.
The global burden of kidney disease is increasing, and several etiologies first begin in childhood. Risk factors for pediatric kidney disease are common in Africa, but data regarding its prevalence are lacking. We completed a systematic review of community-based studies describing the prevalence of proteinuria, hematuria, abnormal imaging, or kidney dysfunction among children in sub-Saharan Africa. Medline and Embase were searched. Five hundred twenty-three references were reviewed. Thirty-two references from 9 countries in sub-Saharan Africa were included in the qualitative synthesis. The degree of kidney damage and abnormal imaging varied widely: proteinuria 32.5% (2.2%-56.0%); hematuria 31.1% (0.6%-67.0%); hydronephrosis 11.3% (0.0%-38.0%), hydroureter 7.5% (0.0%-26.4%), major kidney abnormalities 0.1% (0.0%-0.8%). Serum creatinine was reported in four studies with insufficient detail to identify the prevalence renal dysfunction. A majority of the studies were performed in Schistosoma haematobium endemic areas. A lower prevalence of kidney disease was observed in the few studies from non-endemic areas. Published data on pediatric kidney disease in sub-Saharan Africa is highly variable and dependent on S. haematobium prevalence. More community-based studies are needed to describe the burden of pediatric kidney disease, particularly in regions where S. haematobium infection is non-endemic.Pediatric Research (2014); doi:10.1038/pr.2014.189.
- Unusual Cause and Presentation of Collapsing Focal Segmental Glomerulosclerosis. [JOURNAL ARTICLE]
- Am J Ther 2014 Nov 21.
Collapsing focal segmental glomerulosclerosis (c-FSGS), a structural variant of focal segmental glomeruloslecrosis (FSGS), is considered to be the most aggressive FSGS form. Most patients present with severe nephrotic syndrome and often have rapidly progressing renal failure and progression to end-stage kidney disease. We are reporting a 28-year-old previously healthy woman, who was started on griseofulvin for onchomycosis; she subsequently developed acute renal failure with significant proteinuria. Exposure to the drug caused dramatic decline in the renal function. Renal biopsy was compatible with c-FSGS. To the best of our knowledge, this is the first case of biopsy-proven griseofulvin-associated c-FSGS. Our patient showed rapid improvement in renal function after discontinuation of griseofulvin. Universally, c-FSGS carries poor prognosis, but this case is unique because patient showed rapid improvement in renal function with a short duration after cessation of griseofulvin.
- Long-term risk of chronic kidney disease and mortality in children after acute kidney injury: a systematic review. [JOURNAL ARTICLE]
- BMC Nephrol 2014 Nov 21; 15(1):184.
Acute kidney injury (AKI) is associated with significant short-term morbidity and mortality in children. However, the risk for long-term outcomes after AKI is largely unknown.We performed a systematic review and meta-analysis to determine the cumulative incidence rate of proteinuria, hypertension, decline in glomerular filtration rate (GFR), and mortality after an episode of AKI. After screening 1934 published articles from 1985-2013, we included 10 cohort studies that reported long-term outcomes after AKI in children.A total of 346 patients were included in these studies with a mean follow-up of 6.5 years (range 2-16) after AKI. The studies were of variable quality and had differing definitions of AKI with five studies only including patients who required dialysis during an AKI episode. There was a substantial discrepancy in the outcomes across these studies, most likely due to study size, disparate outcome definitions, and methodological differences. In addition, there was no non-AKI comparator group in any of the published studies. The cumulative incidence rates for proteinuria, hypertension, abnormal GFR (<90 ml/min/1.73 m2), GFR < 60 ml/min/1.73 m2, end stage renal disease, and mortality per 100 patient-years were 3.1 (95% CI 2.1-4.1), 1.4 (0.9-2.1), 6.3 (5.1-7.5), 0.8 (0.4 -1.4), 0.9 (0.6-1.4), and 3.7 (2.8-4.5) respectively.AKI appears to be associated with a high risk of long-term renal outcomes in children. These findings may have implications for care after an episode of AKI in children. Future prospective studies with appropriate non-AKI comparator groups will be required to confirm these results.