A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of an Omega-3 Fatty Acid Supplement in Patients With Predialysis Chronic Kidney Disease.

OBJECTIVE: Omega-3 fatty acids may reduce albuminuria and cardiovascular risk factors in patients with chronic kidney disease (CKD). We aimed to assess the effects of omega-3 fatty acid supplementation on albuminuria, blood pressure, pulse wave velocity, and inflammatory markers in patients with CKD. METHODS: Patients with CKD and a urine albumin excretion of at least 30 mg/g creatinine were supplemented for 3 months with 3,666 mg/day of docosahexaenoic and eicosapentaenoic acids or a corn oil supplement. The study was double blind. At baseline, 6 weeks, and 12 weeks, fasting blood and morning spot urine samples were obtained. Blood pressure, carotid intima media thickness, and pulse wave velocity were measured. The main outcome measure was a reduction of ≥20% in urine albumin. RESULTS: One hundred patients were randomized (50 received omega-3 fatty acids and 50 received corn oil). Four patients who received omega-3 fatty acids and 5 who received vegetable oil were lost to follow-up. In patients receiving omega-3 fatty acids, the omega-3 index increased from 3.08 (2.32-3.81) to 5.48 (3.045-7.04) percent. A 20% reduction in urine albumin excretion was observed in 13 participants of the control group and 19 participants of omega-3 group (Fisher's exact P = .274). However, the supplement had a significant and positive effect on pulse wave velocity and triglyceride level. CONCLUSION: An omega-3 fatty acid supplement of 3,666 mg/day did not modify urine albumin excretion in patients with CKD but did improve pulse wave velocity and serum triglyceride levels.

Metformin arrests the progression of established kidney disease in the subtotal nephrectomy model of chronic kidney disease.

Metformin, an AMP-activated protein kinase (AMPK) activator, has been shown in previous studies to reduce kidney fibrosis in different models of experimental chronic kidney disease (CKD). However, in all of these studies, the administration of metformin was initiated before the establishment of renal disease, which is a condition that does not typically occur in clinical settings. The aim of the present study was to investigate whether the administration of metformin could arrest the progression of established renal disease in a well-recognized model of CKD, the subtotal kidney nephrectomy (Nx) model. Adult male Munich-Wistar rats underwent either Nx or sham operations. After the surgery (30 days), Nx rats that had systolic blood pressures of >170 mmHg and albuminuria levels of >40 mg/24 h were randomized to a no-treatment condition or to a treatment condition with metformin (300 mg·kg-1·day-1) for a period of either 60 or 120 days. After 60 days of treatment, we did not observe any differences in kidney disease parameters between Nx metformin-treated and untreated rats. However, after 120 days, Nx rats that had been treated with metformin displayed significant reductions in albuminuria levels and in markers of renal fibrosis. These effects were independent of any other effects on blood pressure or glycemia. In addition, treatment with metformin was also able to activate kidney AMPK and therefore improve mitochondrial biogenesis. It was concluded that metformin can arrest the progression of established kidney disease in the Nx model, likely via the activation of AMPK.

Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial

Background Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods REWIND was a multicenter, randomized, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m² (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1­5·9) comprising 51 820 person years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77­0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68­0·87; p<0·0001), with HRs of 0·89 (0·78­1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39­1·44; p=0·39) for chronic renal replacement therapy. (AU)

Unsweetening the Heart: Possible Pleiotropic Effects of SGLT2 Inhibitors on Cardio and Cerebrovascular Alterations in Resistant Hypertensive Subjects.

Resistant hypertension (RH) is a multifactorial disease associated with several target organ damage, such as microalbuminuria, left ventricular hypertrophy, and arterial stiffness. These subjects have high cardiovascular complications, especially when associated with diabetes condition. Sodium glucose cotransporter 2 (SGLT-2) inhibitors represent a new class of oral antidiabetic drugs that have shown positive effects in diabetics and even hypertensives subjects. Several studies demonstrated positive outcomes related to blood pressure levels, body weight, and glycemic control. Also found a reduction on microalbuminuria, cardiac and arterial remodeling process, and decrease in hospitalization care due heart failure. Despite these positive effects, the outcomes found for stroke were conflicted and tend neutral effect. Based on this, we sought to assess the pleiotropic effects of SGLT-2 inhibitors and the possible impact in RH subjects. In order to analyze the prospects of SGLT-2 inhibitors as a possible medication to complement the therapy manage of this high-risk class of patients.

A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy.

Aldosterone antagonists slow the progression of chronic kidney disease (CKD), but their use is limited by hyperkalemia, especially when associated with RAS inhibitors. We examined the renoprotective effects of Ly, a novel non-steroidal mineralocorticoid receptor (MR) blocker, through two experimental protocols: In Protocol 1, male Munich-Wistar rats underwent 5/6 renal ablation (Nx), being divided into: Nx+V, receiving vehicle, Nx+Eple, given eplerenone, 150 mg/kg/day, and Nx+Ly, given Ly, 20 mg/kg/day. A group of untreated sham-operated rats was also studied. Ly markedly raised plasma renin activity (PRA) and aldosterone, and exerted more effective anti-albuminuric and renoprotective action than eplerenone. In Protocol 2, Nx rats remained untreated until Day 60, when they were divided into: Nx+V receiving vehicle; Nx+L treated with losartan, 50 mg/kg/day; Nx+L+Eple, given losartan and eplerenone, and Nx+L+Ly, given losartan and Ly. Treatments lasted for 90 days. As an add-on to losartan, Ly normalized blood pressure and albuminuria, and prevented CKD progression more effectively than eplerenone. This effect was associated with strong stimulation of PRA and aldosterone. Despite exhibiting higher affinity for the MR than either eplerenone or spironolactone, Ly caused no hyperkalemia. Ly may become a novel asset in the effort to detain the progression of CKD.

P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

Valor de la microalbuminuria en la detección precoz de la enfermedad renal crónica / Value of microalbuminuria in the early detection of chronic kidney disease

Introducción: la enfermedad renal crónica es un problema de salud a nivel mundial y se asocia con factores de riesgo de alta incidencia en nuestra población, entre los que se encuentran la presencia de microalbuminuria, poco estudiada en población sana, al igual que la evaluación de la función renal a través del uso de fórmulas para el cálculo teórico de la tasa de filtración glomerular. Objetivos: caracterizar las variables demográficas y la función renal, así como determinar el valor predictivo de la microalbuminuria y de la disminución del filtrado glomerular en la serie estudiada. Métodos: se realizó un estudio observacional, analítico y de corte transversal, en el Hospital Militar Central Dr. Luis Díaz Soto. La serie estuvo constituida por 401 pacientes. Se empleó el test de microalb látex para determinar la presencia de microalbuminuria y la fórmula MDRD-IDMS para estimar el filtrado glomerular. Resultados: la presencia de microalbumiuria se constató en el 22,94 por ciento (n = 92) de la serie. De los microalbuminúricos, el 61,95 por ciento (n = 57) correspondió con el grupo etario entre 20 y 39 años, predominó el color de la piel blanca para el 41,30 por ciento (n = 38), y se clasificó en estadio I y II de enfermedad renal crónica el 12,96 por ciento (n = 52) y el 9,97 por ciento (n = 40), respectivamente.Conclusiones: la microalbuminuria es un factor de riesgo con valor predictivo en estadios iniciales de la enfermedad renal crónica, en edades tempranas(AU)

Introduction: chronic kidney disease is a health problem worldwide and it is associated with high incidence of risk factors in our population, such as the presence of microalbuminuria, which has been little studied in healthy people, as well as the evaluation of the renal function through the use of theoretical calculating formulas of the glomerular filtration rate. Objectives: to characterize the demographic variables and renal function, to determine the predictive value of microalbuminuria and reduced glomerular filtration rate in the present series. Methods: an observational, analytical and cross section studied was carried out at Dr. Luis DÝaz Soto Central Military Hospital. The series consisted of 401 patients. Latex microlab test was used to determine microalbuminuria and GFR was estimated by MDRD-IDMS formula. Results: the presence of microalbumiuria was found in 22.94 percent (n = 92) of the series. Out of the patients with microalbuminuria, 61.95 percent (n = 57) aged 20-39 years old. 41.30 percent (n = 38) patients were white. Stages I and II were classified of chronic kidney 12.96 percent (n = 52) and 9.97 percent (n = 40), respectively. Conclusions: microalbuminuria is a risk factor with predictive value in early stages of chronic kidney disease at an early age(AU)

[Efect of short term glycemic control on microalbuminuria and glomerular filtration rate in type 2 diabetic patients with poor glycemic control]. / Efeitos do controle glicêmico obtido em curto prazo sobre a microalbuminúria e a filtração glomerular em pacientes diabéticos do tipo 2 com controle glicêmico precário.

INTRODUCTION: The intensive glucose control significantly reduces the risk of microvascular complications, including nephropathy. OBJECTIVES: We assess the impact of glycemic control through calculation of weekly mean glycemia (WMG) and glycemic variability (GV) on 24 hours ambulatory blood pressure (ABPM), urinary albumin excretion (UAE) and glomerular filtration rate (GFR). METHODS: 53 patients with type 2 diabetes mellitus (DM2) were randomly divided into two groups to receive conventional or intensive treatment, which included weekly visits for medication adjustments and implementation of an educational plan for six weeks. RESULTS: We observed glycemic control (WMG < 150 mg/dL and VG < 50) in 75% (n = 21) of the patients on the intervention treatment (IT) (n = 28), and in 24% (n = 6) of the ones on the conventional treatment (CT) (n = 25) (p < 0.001). Considering patients of the two groups, 14 out of the 27 patients who achieved glycemic control showed initial mean systolic blood pressure (SBP) > 120 mmHg which was reduced from 138.4 ± 10.1 to 127.8 ± 11.6 mmHg (p = 0.023) at the end of week six. Reductions in SBP and diastolic BP (DBP) during wakefulness and sleep did not occur in the group (n = 17) without glycemic control and with SBP > 120 mmHg. Initially, 15 patients had GFR > 120 mL/min, and after six weeks, only the subgroup that achieved glycemic control (n = 7) showed a reduction of 137.2 ± 16 to 122.2 ± 25.2 mL/min (p = 0.02). At the beginning of the study, another fifteen patients presented with microalbuminuria. After six weeks, regardless of whether they achieved glycemic control or not, there was reduction in UAE, from 63.0 ± 43.1 to 24.8 ± 19.5 mg/g creatinine (p = 0.02). CONCLUSION: Thus short term glycemic control resulted in reductions of BP, GFR and the UAE in patients with DM2, which are beneficial for renal protection.

Efeitos do controle glicêmico obtido em curto prazo sobre a microalbuminúria e a filtração glomerular em pacientes diabéticos do tipo 2 com controle glicêmico precário / Efect of short term glycemic control on microalbuminuria and glomerular filtration rate in type 2 diabetic patients with poor glycemic control

INTRODUÇÃO: O controle intensivo da glicemia reduz significativamente o risco de desenvolvimento de complicações microvasculares, incluindo a nefropatia. OBJETIVOS: Foi avaliado o impacto do controle glicêmico, por meio do cálculo da glicemia média semanal (GMS) e variabilidade glicêmica (VG), sobre a pressão arterial (PA) nas 24 horas (MAPA), excreção urinária de albumina (EUA) e taxa de filtração glomerular (TFG). MÉTODOS: 53 pacientes com diabetes mellitus tipo 2 (DM2), dividida aleatoriamente em dois grupos para receber tratamento convencional ou intensivo. Esse último incluía visitas semanais para ajustes da medicação e aplicação de um plano educacional durante seis semanas. RESULTADOS: Observou-se controle glicêmico (GMS < 150 mg/dL e VG < 50) em 75% (n = 21) dos pacientes do grupo intervenção (GI) (n = 28) e em 24% (n = 6) do grupo convencional (GC) (n = 25) (p < 0,001). Dos 27 pacientes dos dois grupos que obtiveram controle glicêmico, 14 apresentavam inicialmente média da PA sistólica (PAS) > 120 mmHg e que se reduziu de 138,4 ± 10,1 para 127,8 ± 11,6 mmHg (p = 0,023) ao final das seis semanas. Foram observadas reduções da PAS e PA diastólica (PAD) na vigília e durante o sono, que não ocorreram no grupo (n = 17) sem controle glicêmico e PAS >120 mmHg. Inicialmente, 15 pacientes apresentavam TFG >120 mL/min, sendo que após seis semanas, apenas o subgrupo que alcançou controle glicêmico (n = 7) mostrou redução de 137,2 ± 16 para 122,2 ± 25,2 mL/min (p = 0,02). No inicio do estudo, outros quinze pacientes apresentavam microalbuminúria. Após seis semanas, independente de terem alcançado o controle glicêmico preconizado, observou-se redução da EUA de 63,0 ± 43,1 para 24,8 ± 19,5 mg/g de creatinina (p = 0,02). CONCLUSÃO: Assim, o controle glicêmico obtido em curto prazo resultou na redução da PA, da TFG e da EUA nos pacientes com DM2 que apresentavam alterações desses parâmetros, alterações benéficas no que se refere à proteção renal.

INTRODUCTION: The intensive glucose control significantly reduces the risk of microvascular complications, including nephropaty. OBJECTIVES: We assess the impact of glycemic control through calculation of weekly mean glycemia (WMG) and glycemic variability (GV) on 24 hours ambulatory blood pressure (ABPM), urinary albumin excretion (UAE) and glomerular filtration rate (GFR). METHODS: 53 patients with type 2 diabetes mellitus (DM2) were randomly divided into two groups to receive conventional or intensive treatment, which included weekly visits for medication adjustments and implementation of an educational plan for six weeks. RESULTS: We observed glycemic control (WMG < 150 mg/dL and VG < 50) in 75% (n = 21) of the patients on the intervention treatment (IT) (n = 28), and in 24% (n = 6) of the ones on the conventional treatment (CT) (n = 25) (p < 0.001). Considering patients of the two groups, 14 out of the 27 patients who achieved glycemic control showed initial mean systolic blood pressure (SBP) > 120 mmHg which was reduced from 138.4 ± 10.1 to 127.8 ± 11.6 mmHg (p = 0.023) at the end of week six. Reductions in SBP and diastolic BP (DBP) during wakefulness and sleep did not occur in the group (n = 17) without glycemic control and with SBP > 120 mmHg. Initially, 15 patients had GFR > 120 mL/min, and after six weeks, only the subgroup that achieved glycemic control (n = 7) showed a reduction of 137.2 ± 16 to 122.2 ± 25.2 mL/min (p = 0.02). At the beginning of the study, another fifteen patients presented with microalbuminuria. After six weeks, regardless of whether they achieved glycemic control or not, there was reduction in UAE, from 63.0 ± 43.1 to 24.8 ± 19.5 mg/g creatinine (p = 0.02). CONCLUSION: Thus short term glycemic control resulted in reductions of BP, GFR and the UAE in patients with DM2, which are beneficial for renal protection.

Microalbuminuria y excreción urinaria de albúmina en la práctica clínica / Microalbuminuria and urinary albumin excretion in clinical practice

Background: Microalbuminuria is a new tool in the management of patients with diabetes mellitus or hypertension. Microalbuminuria is an easily measured biomarker in a urine sample. Urinary albumin to creatinine ratio in first morning urine sample correlates with 24 hours urinary albumin excretion, but it is easier to obtain, and can identify hypertensive or diabetic patients with high risk for cardiovascular events. Therapeutic interventions such as renin angiotensin system blockade have demonstrated their usefulness in reducing urinary albumin excretion in clinical studies. It would be advisable to incorporate urinary albumin to creatinine ratio to the routine clinical monitoring of patients with cardiovascular risk, such as those with hypertension and diabetes mellitus.

Beneficial effect of ubiquinol, the reduced form of coenzyme Q10, on cyclosporine nephrotoxicity.

BACKGROUND: Cyclosporine (CyA) nephrotoxicity is partly due to some oxidative stress. Ubiquinol, the reduced form of coenzyme Q10 (rCoQ10), has recently gained attention for its anti-oxidative potential. The aim of this study is to evaluate the effect of rCoQ10 on a CyA nephrotoxic rat model. MATERIALS AND METHODS: Six-week-old male Wistar rats were divided into three groups (five animals each). Group 1 received a medium only. Group 2 received 30 mg/kg/day of CyA only. Group 3 received both the same dose of CyA and 600 mg/kg/day of rCoQ10. CyA and rCoQ10 were both given orally for four weeks. Systolic blood pressure (BP), daily urinary albumin secretion (u-Alb), serum creatinine (s-Cr) level, and super-oxide anion (SO) level in the renal tissue were measured and compared among those three groups. Immunohistochemistry using an antibody for the transforming growth factor-beta (TGF-beta) was also examined. RESULTS: BPs, u-Albs, s-Crs, and SO levels of groups 1, 2, and 3 were 114 ± 3, 132 ± 4, and 129 ± 5 mmHg, 2.6 ± 0.5, 42.1 ± 7.2, and 22.8 ± 3.4 micro-g/day, 1.1 ± 0.2, 1.7 ± 0.2, and 1.3 ± 0.2 mg/dL, and 224 ± 84, 1251 ± 138, and 512 ± 109 RLU/g kidney respectively. U-Albs, s-Crs, and SO levels were signifi cantly ameliorated by rCoQ10. Micro-vacuolar changes and TGF-beta positive deposits in the proximal renal tubular cells of CyA group rats disappeared in those of CyA and rCoQ10 group rats. CONCLUSION: RCoQ10, an antioxidants, may have potential for preventing CyA nephrotoxicity.

Tempol reduces podocyte apoptosis via PARP signaling pathway in experimental diabetes mellitus.

BACKGROUND/AIMS: In diabetic hypertensive rats, tempol reduces albuminuria by restoring the redox imbalance. Increased formation of reactive oxygen species leading to activation of poly(ADP-ribose) polymerase (PARP)-1 and podocyte loss by apoptosis contribute to albuminuria in diabetes mellitus (DM). In the present study, we investigated the hypothesis that in DM tempol reduces albuminuria by inhibition of PARP-induced podocyte apoptosis. METHODS: DM was induced in 4-week-old spontaneously hypertensive rats by streptozotocin. Mouse and human podocyte cell lines were cultured in normal or high-glucose conditions, with or without tempol and/or a PARP-1 inhibitor, PJ34. RESULTS: In diabetic rats, tempol treatment did not affect plasma glucose levels or systolic blood pressure. Albuminuria was higher in diabetic rats, and it was reduced by tempol. DM leads to an elevation of glomerular apoptotic cells and to podocyte loss; both were prevented by tempol treatment. DM increases the expression of poly(ADP-ribose)-modified proteins in isolated glomeruli, and it was reduced by tempol. In vitro, high glucose increased caspase-3 activity and led to a higher number of apoptotic cells that were prevented by tempol and the PARP-1 inhibitor. CONCLUSION: In DM, tempol reduces albuminuria associated with reduction of podocyte apoptosis and decreasing oxidative stress via PARP signaling.

Beneficial effect of ubiquinol, the reduced form of coenzyme Q10, on cyclosporine nephrotoxicity

BACKGROUND: Cyclosporine (CyA) nephrotoxicity is partly due to some oxidative stress. Ubiquinol, the reduced form of coenzyme Q10 (rCoQ10), has recently gained attention for its anti-oxidative potential. The aim of this study is to evaluate the effect of rCoQ10 on a CyA nephrotoxic rat model. MATERIALS AND METHODS: Six-week-old male Wistar rats were divided into three groups (five animals each). Group 1 received a medium only. Group 2 received 30 mg/kg/day of CyA only. Group 3 received both the same dose of CyA and 600 mg/kg/day of rCoQ10. CyA and rCoQ10 were both given orally for four weeks. Systolic blood pressure (BP), daily urinary albumin secretion (u-Alb), serum creatinine (s-Cr) level, and super-oxide anion (SO) level in the renal tissue were measured and compared among those three groups. Immunohistochemistry using an antibody for the transforming growth factor-beta (TGF-beta) was also examined. RESULTS: BPs, u-Albs, s-Crs, and SO levels of groups 1, 2, and 3 were 114 ± 3, 132 ± 4, and 129 ± 5 mmHg, 2.6 ± 0.5, 42.1 ± 7.2, and 22.8 ± 3.4 micro-g/day, 1.1 ± 0.2, 1.7 ± 0.2, and 1.3 ± 0.2 mg/dl, and 224 ± 84, 1251 ± 138, and 512 ± 109 RLU/g kidney respectively. U-Albs, s-Crs, and SO levels were significantly ameliorated by rCoQ10. Micro-vacuolar changes and TGF-beta positive deposits in the proximal renal tubular cells of CyA group rats disappeared in those of CyA and rCoQ10 group rats. CONCLUSION: RCoQ10, an antioxidants, may have potential for preventing CyA nephrotoxicity.

Weight loss improves renal hemodynamics in patients with metabolic syndrome.

OBJECTIVE: We investigated the impact of weight loss on urinary albumin excretion (UAE) and creatinine clearance in obese patients with metabolic syndrome. METHODS: Thirty-five obese patients undertook a 12-week calorie-restricted diet. The patients underwent a metabolic (oral glucose tolerance test, plasma lipids, and uric acid) and renal hemodynamic evaluations (creatinine clearance and urinary albumin excretion) before (phase 1), and after the 12-week diet (phase 2). RESULTS: After the dietary intervention, the subjects were divided into two groups: patients who achieved the target weight reduction (R: responders, n = 14), and patients who did not (NR: non-responders, n = 21). The patients in Group R showed an improvement in lipid profile, a decrease in UAE (median = 162.5 mg/24 hours, range: 0.8 to 292 mg/24 hours, at phase 1 versus 10.4 mg/24 hours, range: 1.6 to 22.4 mg/24 hours, at phase 2), and a significant reduction in creatinine clearance (121.4 ± 66.5 mL/min. in phase 1 to 92.9 ± 35.6 mL/min. at the end of phase 2, p = 0.001). In Group NR, no statistically significant differences were observed between phases 1 and 2. CONCLUSION: Body weight reduction has a positive impact on renal hemodynamics, decreasing urinary albumin excretion as well as glomerular hyperfiltration in obese patients with metabolic syndrome.

Efeito da perda de peso sobre a hemodinâmica renal em portadores da síndrome metabólica / Weight loss improves renal hemodynamics in patients with metabolic syndrome

OBJETIVO: No presente artigo, investigou-se o impacto da redução do peso corporal na excreção urinária de albumina e na depuração da creatinina em indivíduos obesos com síndrome metabólica. MÉTODOS: Trinta e cinco indivíduos foram submetidos à dieta hipocalórica por um período de 12 semanas, visando uma redução mínima de 5% do peso corporal. Os voluntários foram submetidos à avaliação metabólica (teste oral de tolerância à glicose, dosagens de lípides plasmáticos e ácido úrico) e à avaliação de parâmetros hemodinâmicos renais (depuração da creatinina e excreção urinária de albumina), antes (fase 1) e após 12 semanas de dieta hipocalórica (fase 2). RESULTADOS: Após o período de intervenção, os voluntários foram divididos em dois grupos: indivíduos que atingiram o alvo para redução de peso (respondedores: R, n = 14) e pacientes que não atingiram a meta para redução de peso (não-respondedores: NR, n = 21). Indivíduos do Grupo R apresentaram melhora do perfil lipídico, da redução da excreção urinária de albumina (mediana = 162.5 mg/24 horas, variação: 0,8 a 292 mg/24 horas, na fase 1 para 10,4 mg/24 horas, variação: 1,6 a 22,4 mg/24 horas, na fase 2), além de redução significante da depuração da creatinina (121,4 ± 66,5 mL/min. para 92,9 ± 35,6 mL/min., p = 0,001). No Grupo NR, não foram observadas diferenças estatisticamente significantes entre as fases 1 e 2 do estudo. CONCLUSÃO: A redução do peso corporal teve impacto positivo na hemodinâmica renal, reduzindo a excreção urinária de albumina e a hiperfiltração glomerular em indivíduos obesos com síndrome metabólica.

OBJECTIVE: We investigated the impact of weight loss on urinary albumin excretion (UAE) and creatinine clearance in obese patients with metabolic syndrome. METHODS: Thirty-five obese patients undertook a 12-week calorie-restricted diet. The patients underwent a metabolic (oral glucose tolerance test, plasma lipids, and uric acid) and renal hemodynamic evaluations (creatinine clearance and urinary albumin excretion) before (phase 1), and after the 12-week diet (phase 2). RESULTS: After the dietary intervention, the subjects were divided into two groups: patients who achieved the target weight reduction (R: responders, n = 14), and patients who did not (NR: non-responders, n = 21). The patients in Group R showed an improvement in lipid profile, a decrease in UAE (median = 162.5 mg/24 hours, range: 0.8 to 292 mg/24 hours, at phase 1 versus 10.4 mg/24 hours, range: 1.6 to 22.4 mg/24 hours, at phase 2), and a significant reduction in creatinine clearance (121.4 ± 66.5 mL/min. in phase 1 to 92.9 ± 35.6 mL/min. at the end of phase 2, p = 0.001). In Group NR, no statistically significant differences were observed between phases 1 and 2. CONCLUSION: Body weight reduction has a positive impact on renal hemodynamics, decreasing urinary albumin excretion as well as glomerular hyperfiltration in obese patients with metabolic syndrome.

[Microalbuminuria and urinary albumin excretion in clinical practice]. / Microalbuminuria y excreción urinaria de albúmina en la práctica clínica.

Microalbuminuria is a new tool in the management of patients with diabetes mellitus or hypertension. Microalbuminuria is an easily measured biomarker in a urine sample. Urinary albumin to creatinine ratio in first morning urine sample correlates with 24 hours urinary albumin excretion, but it is easier to obtain, and can identify hypertensive or diabetic patients with high risk for cardiovascular events. Therapeutic interventions such as renin angiotensin system blockade have demonstrated their usefulness in reducing urinary albumin excretion in clinical studies. It would be advisable to incorporate urinary albumin to creatinine ratio to the routine clinical monitoring of patients with cardiovascular risk, such as those with hypertension and diabetes mellitus.

Bradykinin receptor 1 activation exacerbates experimental focal and segmental glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSGS) is one of the most important causes of end-stage renal failure. The bradykinin B1 receptor has been associated with tissue inflammation and renal fibrosis. To test for a role of the bradykinin B1 receptor in podocyte injury, we pharmacologically modulated its activity at different time points in an adriamycin-induced mouse model of FSGS. Estimated albuminuria and urinary protein to creatinine ratios correlated with podocytopathy. Adriamycin injection led to loss of body weight, proteinuria, and upregulation of B1 receptor mRNA. Early treatment with a B1 antagonist reduced albuminuria and glomerulosclerosis, and inhibited the adriamycin-induced downregulation of podocin, nephrin, and α-actinin-4 expression. Moreover, delayed treatment with antagonist also induced podocyte protection. Conversely, a B1 agonist aggravated renal dysfunction and even further suppressed the levels of podocyte-related molecules. Thus, we propose that kinin has a crucial role in the pathogenesis of FSGS operating through bradykinin B1 receptor signaling.

Albuminuria as a marker of kidney and cardio-cerebral vascular damage. Isle of Youth Study (ISYS), Cuba.

INTRODUCTION: The disease complex comprised of atherosclerosis, chronic kidney disease (CKD) and other associated chronic vascular diseases is the leading cause of mortality worldwide. Microalbuminuria is a marker for vascular damage in the heart, kidney and brain. This paper presents selected findings of the clinical-epidemiological Isle of Youth Study (ISYS) of markers for kidney and vascular damage from chronic vascular diseases and their common risk factors in total population, focusing on Phase 2 reassessment (in 2010) of Phase 1 (2004 to 2006) results. OBJECTIVES: (1) Update the prevalence of risk factors in the study population aged ≥20 years (adult population). (2) Confirm presence of microalbuminuria in at-risk adults diagnosed as presumptive positives in Phase I. (3) Evaluate association between microalbuminuria and selected risk factors. METHODS: Of 3779 adults positive for microalbuminuria in ISYS Phase 1, 73.1% were reevaluated. The risk-factor questionnaire was re-administered and blood pressure, weight and height were measured. Blood was tested for creatinine, glycemia, cholesterol and triglycerides. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Albuminuria was measured in urine using Micral-Test (Germany) and albumin/creatinine ratio (ACR) by nephelometry. This paper uses ACR as the reference for analyzing risk factor associations. Double-entry tables were developed to analyze association among microalbuminuria, risk factors and co-morbidities. RESULTS: Most prevalent risks were hypertension, consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), excess weight and hypertriglyceridemia. Microalbuminuria was confirmed in 18% of cases, using the same test. Elevated prevalence of microalbuminuria was positively associated with advancing age, male sex, underweight, smoking, NSAID use, dyslipidemia, hypertension, diabetes, heart disease and stroke. CONCLUSIONS: The at-risk cohort studied presented low levels of confirmation for positive microalbuminuria. Positive microalbuminuria stratified individuals at greatest risk, except for obesity.

[Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes]. / El pentosán polisulfato de sodio previene las alteraciones morfológicas renales y la albuminuria en ratas con diabetes tipo 1.

Decreased levels of glycosaminoglycans (GAGs) have been observed in the kidney and other organs, in human and animal models of diabetes. Long-term administration of heparins and other glycosaminoglycans has demonstrated a beneficial effect on morphological and functional kidney abnormalities in diabetic rats. We assessed the effect of pentosan polysulfate sodium (PPS), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on kidney involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague-Dawley rats by i.v. administration of streptozotocin (STZ). Animals were randomly allocated to three groups: C = control, STZ and STZ + PPS = pretreated with PPS (15 mg/kg, s.c.). After three months of follow-up, blood and 24 h-urine samples were obtained, the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinary albumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs STZ = 7.75 ± 1.8 mg/24 h) and PPS treatment partially prevented the albumin rise (3.7 ± 0.7 mg/24 h), without affecting the metabolic control HbA1c (C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + PPS = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). PPS administration prevents the tubular basement membrane thickening and the loss of cytoarchitecture induced by experimental diabetes. Our data demonstrate that long-term administration of PPS has a favourable effect on morphological and functional abnormalities in kidneys of diabetic rats and suggests a potential therapeutic use for this compound.

Early brief treatment with losartan plus mycophenolate mofetil provides lasting renoprotection in a renal ablation model.

BACKGROUND: Inflammatory events antecede established renal injury in rats with 5/6 renal ablation (Nx), as indicated by the beneficial effects of early, uninterrupted treatment with mycophenolate mofetil (MMF). Angiotensin II also exerts a major pathogenic role at this initial phase. We investigated whether losartan (L) or L+MMF treatment, started early, and L+MMF treatment, started late, would exert lasting renoprotection in Nx even after being discontinued. METHODS: Adult male Munich-Wistar rats underwent Nx and were divided into three groups: Nx (untreated), Nx(L) (given L), and Nx(LMMF) (given L and MMF). Protocol 1: treatments began on day 1, and ceased on day 30, after Nx. Protocol 2: L+MMF treatment began on day 30 and ceased on day 60. RESULTS: Protocol 1: on day 30, hypertension, albuminuria and renal injury were strongly attenuated in Groups Nx(L) and Nx(LMMF). On day 120, these abnormalities were still attenuated in group Nx(LMMF). Protocol 2: on day 120, all parameters were similar between this late Nx(LMMF) group and untreated Nx. CONCLUSION: In Nx, temporary suppression of early, transitory hemodynamic/inflammatory phenomena affords relatively durable renoprotection even after treatment discontinuation. This effect is not obtained with similar temporary treatment initiated later in the course of renal disease.