Differential effects of calcium channel blockers on size selectivity of proteinuria in diabetic glomerulopathy

Differential effects of calcium channel blockers on size selectivity of proteinuria in diabetic glomerulopathy.BackgroundCalcium channel blockers (CCBs) are known to have differential effects on both changes in proteinuria as well as progression of diabetic nephropathy. No clinical study, however, has evaluated whether the differential antiproteinuric effects of CCBs may be explained by their effect on glomerular membrane permeability. We, therefore, tested the hypothesis that certain subclasses of CCBs reduce proteinuria by changing size selectivity of the glomerular membrane, hence changing its permeability.MethodsTwenty-one patients with type 2 diabetes and the presence of nephropathy with hypertension were randomized to receive either diltiazem CD or nifedipine GITS after baseline data for mean systolic and diastolic pressure, urinary protein excretion, glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearances were obtained. Glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearance were measured every three months, arterial pressure and heart rate every month. Patients were followed for 21months.ResultsAt 21months, both patient groups had similar levels of blood pressure control, however, only the diltiazem group had a change in proteinuria (4 ± 10%Δ, nifedipine vs. -57 ± 18%Δ, diltiazem; P < 0.001) with improvement in glomerular size selectivity and change in IgG clearance.ConclusionsThese data support the hypothesis that CCBs that provide sustained reductions in proteinuria do so, in part, by improving glomerular size permselectivity

Effect of Blood Pressure Control on Long-Term Risk of End-Stage Renal Disease and Death Among Subgroups of Patients With Chronic&nbsp;Kidney Disease.

Background Our objective was to explore the effect of intensive blood pressure (BP) control on kidney and death outcomes among subgroups of patients with chronic kidney disease divided by baseline proteinuria, glomerular filtration rate, age, and body mass index. Methods and Results We included 840 MDRD (Modification of Diet in Renal Disease) trial and 1067 AASK (African American Study of Kidney Disease and Hypertension) participants. We used Cox models to examine whether the association between intensive BP control and risk of end-stage renal disease (ESRD) or death is modified by baseline proteinuria (≥0.44 versus &lt;0.44&nbsp;g/g), glomerular filtration rate (≥30 versus &lt;30&nbsp;mL/min per 1.73&nbsp;m2), age (≥40 versus &lt;40&nbsp;years), or body mass index (≥30 versus &lt;30&nbsp;kg/m2). The median follow-up was 14.9&nbsp;years. Strict (versus usual) BP control was protective against ESRD (hazard ratio [HR]ESRD, 0.77; 95% CI, 0.64-0.92) among those with proteinuria ≥0.44&nbsp;g/g but not proteinuria &lt;0.44&nbsp;g/g. Strict (versus usual) BP control was protective against death (HRdeath, 0.73; 95% CI, 0.59-0.92) among those with glomerular filtration rate &lt;30&nbsp;mL/min per 1.73&nbsp;m2 but not glomerular filtration rate ≥30&nbsp;mL/min per 1.73&nbsp;m2 (HRdeath, 0.98; 95% CI, 0.84-1.15). Strict (versus usual) BP control was protective against ESRD among those ≥40&nbsp;years (HRESRD, 0.82; 95% CI, 0.71-0.94) but not &lt;40&nbsp;years. Strict (versus usual) BP control was also protective against ESRD among those with body mass index ≥30&nbsp;kg/m2 (HRESRD, 0.75; 95% CI, 0.61-0.92) but not body mass index &lt;30&nbsp;kg/m2. Conclusions The ESRD and all-cause mortality benefits of intensive BP lowering may not be uniform across all subgroups of patients with chronic kidney disease. But intensive BP lowering was not associated with increased risk of ESRD or death among any subgroups that we examined

Le paludisme urbain à Yaoundé (Cameroun) : 2. Etude entomologique dans deux quartiers peu urbanisés

International audienceA one year entomological survey was carried out to precise the malaria vectors and the malaria transmission in Yaounde, the Cameroon capital (800,000 inhabitants). The study was done in two districts not yet fully urbanized: Nkol Bikok and Nkol Bisson. The latter is located at the periphery and has a pool. Anopheles gambiae was the only human malaria vector. Its agressivity for man depended on the urbanization of the district. Annual man biting rate was 284 in Nkol Bikok and 1,813 in Nkol Bisson. The densities were maximum in May-June and in October-November, corresponding to the end of the short and long rainy seasons. The presence of A. gambiae was permanent except in August-September in Nkol Bikok. In Nkol Bisson the density was higher in the houses near the pool. The yearly inoculation rate (h) was 14 in Nkol Bikok and 30 in Nkol Bisson. The vectorial transmission was observed in may in Nkol Bikok and during four months (June, August, January, February) in Nkol Bisson. These entomological data showed clearly that malaria transmission actually occurred in Yaounde and that the probability to receive at least one infected anopheline bite per year was very near to 1 for inhabitants unprotected against mosquito bites.Une étude longitudinale basée sur la capture des moustiques sur sujets humains s'est déroulée pendant un an dans deux quartiers de la ville de Yaoundé, l'un est situé à la périphérie de la ville (Nkol Bisson) et l'autre est plus central (Nkol Bikok). Ces deux quartiers présentent encore un caractère périurbain mais ils sont en pleine urbanisation. Le vecteur du paludisme humain identifé est Anopheles gambiae. Sa densité agressive pour l'homme (ma) est variable selon le degré d'urbanisation des quartiers : forte en Zone périphérique (ma annuel = I 813) et faible en zone centrale (ma annuel = 284). Cette densité est importante de mai à juin et d'octobre 6 novembre, c'est-à-dire à la fin de la petite et de la grande saison des pluies. Le taux d'inoculation (h) varie comme les densités agressives : h annuel = 30 en zone périphérique contre 14 en zone centrale. La transmission vectorielle est notable seulement pendant un mois (mai) à Nkol Bikok et pendant quatre mois (juin, août, janvier, février) à Nkol Bisson. Le risque quotidien d'au moins une inoculation par A. gambiae est environ deux fois plus élevé en zone périphérique qu'en zone centrale

STUDI EVALUASI DAN RENOVASI SISTEM PENTANAHAN DI SEKOLAH MENENGAH KEJURUAN (SMK) NEGERI 1 CIMAHI

This research is a follow-up to the findings of the inspection and grounding testing in PKM 2018 activities. The value obtained exceeds 5 ohms. This is not according to the standards based on the General Requirements for Electrical Installation (PUIL) 2011. In the 2019 PKM program activities, evaluation and renovation studies of the installed earthing system which includes: surveying the location to be grounded, drilling for the position of the electrodes to be installed, installation of electrodes equipped with Bentonic material which functions as a binder so that the electrodes with the ground become one and strong, measurement of the earthing value, perform grounding installation, re-measurement of earthing. The earthing value obtained is much smaller than the previous measurement results of 2.83 ohms in the Electronics Laboratory and 2.72 Ohms at the Automation Laboratory of SMKN 1 Cimahi. It is according to the recommended standard PUIL 2011. The PKM team proposes the management of SMKN 1 Cimahi to carry out a routine maintenance and measurement process twice a year on the newly installed earthing system so that the earthing value remains according to the standard

Anthropophilic mosquitoes and malaria transmission at Edea, Cameroon

International audienceAn entomological study was carried out during 1990 in the town of Edea in the south of Cameroon to study anthropophilic mosquitoes with special reference to malaria transmission. Man-biting mosquitoes were caught regularly during one night each month in two different districts: Bilalang which is a well planned suburb with 160 houses on a hill-top, provided with a piped water supply; and Pongo which is a densely urbanised suburb in a valley. From 188 man-nights 1030 mosquitoes were collected, comprising 700 Culex quinquefasciatus (68%), 262 Anopheles gambiae (25%) and others species (7%) belonging to the genus Anopheles, Mansonia, Culex and Aedes. The estimated annual biting rates of mosquitoes were 811 bites per man in Bilalang and 2,866 in Pongo. The estimated yearly malaria inoculation rates were 3.8 and 30.2 infective bites per man in Bilalang and Pongo, respectively. In different parts of Pongo district much variation existed; extreme values of the estimated yearly inoculation rate were zero and 86.3 in two houses 200 m apart, located on the top of a hill and in the bottom of a valley, respectively. This study is one of the first conducted on malaria transmission in a moderate sized African town; it shows that the mosquito populations are typically urban and differ greatly from rural ones

C-Reactive protein and risk of ESRD: results from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

Background: To better understand a potential association of elevated C-reactive protein (CRP) level with progression of chronic kidney disease (CKD), we examined the relationship of CRP level with the development of end-stage renal disease (ESRD) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Study Design Post hoc analysis of a randomized controlled trial. Setting &#38; Participants: 4,038 patients with type 2 diabetes, CKD, and anemia in TREAT. Predictor: Baseline serum CRP concentrations. Outcomes: The primary outcome was development of ESRD; secondary outcomes included doubling of serum creatinine level, a composite of ESRD/serum creatinine doubling, and a composite of death or ESRD. Measurements: We fit unadjusted and adjusted Cox regression models to test the association of baseline CRP level with time to the development of the outcomes of interest. Results: Mean age of participants was 67 years, 43% were men, and 64% were white. Approximately half (48%) the patients had CRP levels &gt; 3.0 mg/L; 668 patients developed ESRD, and 1,270 developed the composite outcome of death or ESRD. Compared with patients with baseline CRP levels ≤ 3.0 mg/L, those with moderately/markedly elevated CRP levels (≥6.9 mg/L; 24% of patients) had a higher adjusted risk for ESRD (HR, 1.32; 95% CI, 1.07-1.63) and the composite outcome of death or ESRD (HR, 1.41; 95% CI, 1.21-1.64). Although nonsignificant, similar trends were noted in competing-risk models. Limitations: Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia. Conclusions: Elevated baseline CRP levels are common in type 2 diabetic patients with anemia and CKD and are associated with the future development of ESRD and the composite of death or ESRD

Sepsis-Associated Acute Kidney Disease and Long-term Kidney Outcomes

Rationale & Objective: Sepsis-associated acute kidney injury often leads to acute kidney disease (AKD), predisposing patients to long-term complications such as chronic kidney disease (CKD), kidney failure with replacement therapy (KFRT), or mortality. Risk stratification of patients with AKD represents an opportunity to assist with prognostication of long-term kidney complications. Study Design: Single-center retrospective cohort. Setting & Participants: 6,290 critically ill patients admitted to the intensive care unit with severe sepsis or septic shock. Patients were separated into cohorts based on incident acute kidney injury or not, and survivors identified who were alive and free of KFRT up to 90 days. Predictors: AKD stage (0A, 0C, or ≥1) using the last serum creatinine concentration available by discharge or up to 90 days postdischarge. Outcome: Time to development of incident CKD, progression of CKD, KFRT, or death. Analytical Approach: Multivariable Cox proportional hazards models. Results: Patients surviving kidney injury associated with sepsis often fail to return to baseline kidney function by discharge: 577/1,231 (46.9%) with stage 0C or 1 or greater AKD. AKD stage was significantly associated with the composite primary outcome. Stages 0C AKD and 1 or greater AKD were significantly and progressively associated with the primary outcome when compared with stage 0A AKD (adjusted HR [aHR], 1.74; 95% CI, 1.32-2.29, and aHR, 3.25; 95% CI, 2.52-4.20, respectively). Additionally, stage 1 or greater AKD conferred higher risk above stage 0C AKD (aHR, 1.87; 95% CI, 1.44-2.43). CKD incidence or progression and KFRT, more so than mortality, occurred with greater frequency in higher stages of AKD. Limitations: Retrospective design, single center, exclusion of patients with KFRT within 90 days of discharge, potential ascertainment bias, and inability to subclassify above AKD stage 1. Conclusions: Risk stratification using recommended AKD stages at hospital discharge or shortly thereafter associates with the development of long-term kidney outcomes following sepsis-associated acute kidney injury

Baseline urinary metabolites predict albuminuria response to spironolactone in type 2 diabetes

The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in subjects with diabetic kidney disease, albeit with a large variability between individuals. Identifying novel biomarkers that predict response to therapy may help to tailor spironolactone therapy. We aimed to identify a set of metabolites for prediction of albuminuria response to spironolactone in subjects with type 2 diabetes. Systems biology molecular process analysis was performed a priori to identify metabolites linked to molecular disease processes and drug mechanism of action. Individual subject data and urine samples were used from 2 randomized placebo controlled double blind clinical trials (NCT01062763, NCT00381134). A urinary metabolite score was developed to predict albuminuria response to spironolactone therapy using penalized ridge regression with leave-one-out cross validation. Bioinformatic analysis identified a set of 18 metabolites linked to a diabetic kidney disease molecular model and potentially affected by spironolactone mechanism of action. Spironolactone reduced UACR relative to placebo by median -42% (25th to 75% percentile -65 to 6) and -29% (25th to 75% percentile -37 to -1) in the test and replication cohorts, respectively. In the test cohort, UACR reduction was higher in the lowest tertile of the baseline urinary metabolite score compared with middle and upper tertiles -58% (25th to 75% percentile -78 to 33), -28% (25th to 75% percentile -46 to 8), -40% (25th to 75% percentile -52% to 31), respectively, P= 0.001 for trend). In the replication cohort, UACR reduction was -54% (25th to 75% percentile -65 to -50), -41 (25th to 75% percentile -46% to 30), and -17% (25th to 75% percentile -36 to 5), respectively, P= 0.010 for trend). We identified a set of 18 urinary metabolites through systems biology to predict albuminuria response to spironolactone in type 2 diabetes. These data suggest that urinary metabolites may be used as a tool to tailor optimal therapy and move in the direction of personalized medicine

Serum Renin and Major Adverse Kidney Events in Critically Ill Patients: A Multicenter Prospective Study

BACKGROUND: Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. METHODS: Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5-7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline. RESULTS: Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without. CONCLUSIONS: In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality

Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction : the randomized MARLINA-T2D trial

Aims: The MARLINA-T2D study (ClinicalTrials. gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. Methods: A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48-86 mmol/ mol), estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m(2) and urinary albumin-tocreatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time-weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8% +/- 0.9% (62.2 +/- 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60% (-6.6 mmol/mol) (95% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7 mmol/mol]; P Conclusions: In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo-adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.Peer reviewe