Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure

Renal and Cardiovascular Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease: Perspectives on the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial Results

Background: Chronic kidney disease (CKD) risk is elevated in patients with type 2 diabetes mellitus (T2DM). Disease management in these patients has been generally focused on glycemic control and controlling other renal and cardiac risk factors as, historically, few protective therapies have been available. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation -(CREDENCE) trial of canagliflozin was the first study to demonstrate renal protection with a sodium glucose co-transporter 2 inhibitor in patients with T2DM and CKD, and these results could have important implications for clinical practice. Summary: In CREDENCE, participants with T2DM and estimated glomerular filtration rate 30-<90 mL/min/1.73 m2 and urinary albumin-creatinine ratio >300-5,000 mg/g who were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ≥4 weeks prior to randomization at either the maximum labeled or tolerated dose were randomized to receive either canagliflozin 100 mg or placebo. Canagliflozin significantly reduced the risk of the primary composite outcome of doubling of serum creatinine, end-stage kidney disease, or renal or cardiovascular (CV) death compared with placebo (hazard ratio 0.70, 95% CI 0.59-0.82; p = 0.00001). Canagliflozin also reduced the risk of secondary renal and CV outcomes. The safety profile of canagliflozin in CREDENCE was generally similar to previous studies of canagliflozin. No imbalances were observed between canagliflozin and placebo in the risk of amputation or fracture in the CREDENCE population. Key Messages: The positive renal and CV effects of canagliflozin observed in the -CREDENCE trial could have a substantial impact on improving outcomes for patients with T2DM and CKD

The matricial relaxation of a linear matrix inequality

Given linear matrix inequalities (LMIs) L_1 and L_2, it is natural to ask: (Q1) when does one dominate the other, that is, does L_1(X) PsD imply L_2(X) PsD? (Q2) when do they have the same solution set? Such questions can be NP-hard. This paper describes a natural relaxation of an LMI, based on substituting matrices for the variables x_j. With this relaxation, the domination questions (Q1) and (Q2) have elegant answers, indeed reduce to constructible semidefinite programs. Assume there is an X such that L_1(X) and L_2(X) are both PD, and suppose the positivity domain of L_1 is bounded. For our "matrix variable" relaxation a positive answer to (Q1) is equivalent to the existence of matrices V_j such that L_2(x)=V_1^* L_1(x) V_1 + ... + V_k^* L_1(x) V_k. As for (Q2) we show that, up to redundancy, L_1 and L_2 are unitarily equivalent. Such algebraic certificates are typically called Positivstellensaetze and the above are examples of such for linear polynomials. The paper goes on to derive a cleaner and more powerful Putinar-type Positivstellensatz for polynomials positive on a bounded set of the form {X | L(X) PsD}. An observation at the core of the paper is that the relaxed LMI domination problem is equivalent to a classical problem. Namely, the problem of determining if a linear map from a subspace of matrices to a matrix algebra is "completely positive".Comment: v1: 34 pages, v2: 41 pages; supplementary material is available in the source file, or see http://srag.fmf.uni-lj.si

Arterial Stiffness in the Heart Disease of CKD

CKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (, uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD

Low birth weight is associated with chronic kidney disease only in men

The association of low birth weight and chronic kidney disease was examined in a screened volunteer population by the National Kidney Foundation's Kidney Early Evaluation Program. This is a free, community-based health program enrolling individuals aged 18 years or older with diabetes, hypertension, or a family history of kidney disease, diabetes, or hypertension. Self-reported birth weight was categorized and chronic kidney disease defined as an estimated glomerular filtration rate less than 60 ml per min per 1.73 m2 or a urine albumin/creatinine ratio ≥30 mg/g. Among 12 364 participants, 15% reported a birth weight less than 2500 g. In men, significant corresponding odds ratios were found after adjustment for demographic characteristics and health conditions to this low birth weight and chronic kidney disease, but there was no association among women. There was no significant interaction between birth weight and race for either gender. Efforts to clinically understand the etiology of this association and potential means of prevention are essential to improving public health

Impacto da adubação orgânica sobre a incidência de tripes em cebola.

Analisou-se a relação entre adubação orgânica e a incidência de Thrips tabaci Lind. em cebola (Allium cepa L), na EE de Ituporanga,entre agosto e dezembro de 1998. Os tratamentos foram determinados de acordo com a necessidade de N para a cultura pela análise de solo. Empregou-se como fonte orgânica diversos adubos fornecendo 75 Kg/ha de N (esterco suíno; adubo Barriga Verde proveniente de esterco de aves; composto orgânico; esterco de peru; húmus); 37,5 Kg/ha de N (metade da dose normal com esterco de suíno); as testemunhas foram adubação mineral fornecendo 30-120-60 kg/ha de N-P2O5-K2O e o dobro da dose (60-240-120 kg/ha de N-P2O5-K2O); e testemunha sem adubação. Nenhum tratamento apresentou incidência de T. tabaci superior à testemunha sem adubo. A adubação mineral em relação à orgânica não favoreceu significativamente a incidência de T. tabaci . O processo de conversão do manejo do solo da área experimental de convencional para orgânico pode ter favorecido a infestação similar do inseto entre tratamentos. No período de maior incidência de T. tabaci, a relação com nutrientes foi descrita por um modelo envolvendo K/Zn, B e N de maneira positiva. A correlação entre nutrientes e T. tabaci não foi linear na maioria das avaliações. A adubação orgânica pode substituir a adubação mineral na cultura da cebola, pois foi possível atingir níveis de produtividade similares para ambos tratamentos

Discordance between estimated and measured changes in plasma volume among patients with acute heart failure

AIMS: In acute heart failure (AHF), changes of venous haemoglobin (Hb) concentrations, haematocrit (Hct), and estimated plasma volume (ePV) have been proposed as surrogates of decongestion. These estimates are based on the theoretical assumptions that changes of Hb concentrations and Hct are driven by the intravascular volume status and that the intravascular Hb pool remains stable. The objective of this study was to assess the relationship of changes of measured plasma volume (mPV) with changes of Hb, Hct, and ePV in AHF. METHODS AND RESULTS: We studied 36 AHF patients, who received two sequential assessments of mPV, measured red cell volume (mRCV) and measured total blood volume (mTBV) (48 h apart), during the course of diuretic therapy using a novel visible fluorescent injectate (VFI) technique based on the indicator dilution principle. Changes of ePV were calculated based on the Kaplan–Hakim or Strauss formula. AHF patients receiving diuretics (median intravenous furosemide equivalent 160 mg/48 h) displayed a wide range of changes of mPV (−25.4% to +37.0%). Changes in mPV were not significantly correlated with changes of Hb concentration [Pearson's r (r) = −0.241, P = 0.157], Hct (r = −0.307, P = 0.069), ePVKaplan–Hakim (r = 0.228, P = 0.182), or ePVStrauss (r = 0.237, P = 0.163). In contrast to theoretical assumptions, changes of mTBV were poorly correlated with changes of Hb concentrations and some patients displayed unanticipated variability of mRCV, suggesting an unstable intravascular red cell pool. CONCLUSIONS: Changes of Hb or Hct were not reflective of directly measured changes of intravascular volume status in AHF patients. Basing clinical assessment of decongestion on changes of Hb or Hct may misguide clinical decision-making on an individual patient level

Serum creatinine and cystatin C-based estimates of glomerular filtration rate are misleading in acute heart failure

AIMS: We aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation-based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure. METHODS: In this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty-eight patients had two sequential GFR measurements 48 h apart. The co-primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR. RESULTS: VFI-based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker-based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80-0.88, depending on equation used), precision (r(2) , range 0.65-0.78) and accuracy (56%-74% of estimates scored within 30% of mGFR). Correlations of 48-h changes GFR estimates and changes of mGFR were significant (P 15% decrease in mGFR. CONCLUSIONS: In patients hospitalized for acute heart failure, serum creatinine- and cystatin C-based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure