Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease ...onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.
Plasma exposure of the endothelin receptor antagonist atrasentan varies between individuals and is associated with nephroprotective effects and the risk of heart failure. We examined the influence of ...genetic polymorphisms on atrasentan plasma exposure and pharmacodynamic effects. We performed a substudy of the Study of Diabetic Nephropathy With Atrasentan (SONAR) trial which enrolled adults with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate: 25–75 mL/min/1.73 m2, and a urine albumin‐to‐creatinine ratio of 300–5,000 mg/g). Single nucleotide polymorphisms (SNPs) were determined for prespecified membrane transporters, metabolizing enzymes, and the endothelin‐1 peptide. The associations among genotype, atrasentan plasma exposure, and the effect of atrasentan on the prespecified kidney and heart failure hospitalization (HHF) outcomes was assessed with Cox proportional hazards regression models. Of 3,668 patients randomized, 2,329 (63.5%) consented to genotype analysis. Two SNPs in the SLCO1B1 gene (rs4149056 and rs2306283), encoding the hepatic organic anion transporter 1B1 (OATP1B1), showed the strongest association with atrasentan plasma exposure. Based on their SLCO1B1 genotype, patients were classified into normal (atrasentan area under the plasma‐concentration time curve from zero to infinity (AUC0−inf) 41.3 ng·h/mL) or slow (atrasentan AUC0−inf 49.7 ng·h/mL, P < 0.001) OATP1B1 transporter phenotypes. Among patients with a normal OATP1B1 phenotype, the hazard ratio (HR) with atrasentan for the primary kidney and HHF outcomes were 0.61 (95% confidence interval (CI): 0.45–0.81) and 1.35 (95% CI: 0.84–2.13), respectively. In the slow transporter phenotype, HRs for kidney and HHF outcomes were 1.95 (95% CI: 0.95–4.03, P‐interaction normal phenotype = 0.004), and 4.18 (95% CI: 1.37–12.7, P‐interaction normal phenotype = 0.060), respectively. OATP1B1 gene polymorphisms are associated with significant between‐patient variability in atrasentan plasma exposure and long‐term efficacy and safety.
Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was ...associated with long‐term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time‐to‐event models were used to quantify the association between plasma exposure and long‐term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28–0.85) for kidney events and 1.13 (95% CI: 1.03–2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.
OBJECTIVE
The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus ...placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status.
RESEARCH DESIGN AND METHODS
We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200–5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death.
RESULTS
Of 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio HR 0.62 95% CI 0.39, 1.01), prediabetes (HR 0.37 0.21, 0.66), and type 2 diabetes (HR 0.64 0.52, 0.79). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes.
CONCLUSIONS
Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.
The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by ...activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.
Aim
To derive a simple risk score to predict the individual risk of major complications for patients undergoing a percutaneous renal biopsy procedure of native kidneys.
Methods
The risk score was ...derived from a cohort of 1205 adult patients subjected to percutaneous renal biopsy and assigned to training and validation datasets. Factors associated with major complications were derived from univariate analysis and then modelled by stepwise multivariate logistic regression. Based on the odds ratio, independent predictors were assigned a weighted integer. The risk score is calculated from the sum of the integers.
Results
The overall incidence of major complications was 3.2%. Independent factors associated with MC were lower pre‐biopsy haemoglobin, lower platelets, higher blood urea nitrogen, documented chronic kidney disease features in pre‐biopsy ultrasound (US) and the presence of haematoma in the post‐biopsy US. A score for pre‐biopsy evaluation included the first four predictors and stratified patients in three categories with increasing risk at higher scores (low‐risk 0.1%, moderate‐risk 3.0% and high‐risk 26.1%). The score demonstrated good discriminative power (AUC = 0.872). The addition of post‐biopsy US findings increased the discriminative power (AUC = 0.938). A higher post‐biopsy risk score was also associated with a higher incidence of MC (low‐risk 0.2%, moderate‐risk 2.7%, high‐risk 16.9%).
Conclusion
The risk of major complications after a percutaneous renal biopsy can be assessed by a simple risk score calculated from readily available information.
Summary at a Glance
The authors, using experience from a single centre, derive a point based “risk” score, which can aid in determining an individual's risk for a major complication following percutaneous renalbiopsy of the native kidney.
IntroductionBackground: the differences in bioelectrical impedance vector analysis (BIVA) results from different analyzers that use different bioelectrical impedance analysis (BIA) measurement ...technologies are not known. This study aimed to identify the degree of agreement between the BIVA results of four different BIA measurement techniques and to evaluate the degree of agreement between their estimates of fat-free mass (FFM) and fat mass (FM) and those determined by the gold-standard method of dual-energy X-ray absorptiometry (DEXA) in a subgroup of patients without overhydration. Methods: a cross-sectional study was conducted with hemodialysis (HD) patients with end-stage renal disease (ESRD) aged 18 to 65 years. BIA was measured with four different techniques: spectroscopic (BIA-BIS), multifrequency (BIA-MF), single-frequency (BIA-SF), and segmental multifrequency (BIA-MS) techniques. The differences and concordance between the components of the BIA (resistance, reactance, and phase angle) of the four devices were analyzed. Patients with a normal hydration status were identified, and concordance between FM and FFM measurements with each impedance device and DEXA was observed only in these patients. Results: thirty patients were included. The concordance between the components of BIA ranged from good to excellent (phase angle: intraclass correlation coefficient (ICC) = 0.82, 95 % confidence interval (CI): 0.77-0.93; resistance: ICC = 0.98, 95 % CI: 0.92-0.99). The overall concordance for BIVA diagnosis between the analyzers was substantial for hydration (k = 0.71, 95 % CI: 0.71-0.72) and for body tissues (k = 0.68, 95 % CI: 0.67-0.68). Bland-Altman plots showed the lowest bias between BIA-BIS and DEXA for both FM and FFM. Conclusions: the agreement among the four devices was good for diagnosis by BIVA. The BIA-BIS analyzer and DEXA had the lowest bias for both FFM and FM, although with higher limits of agreement. The lowest limits of agreement were found with the BIA-MS analyzer.
Introduction
Peritoneal dialysis (PD) guidelines recommend a 14‐day break‐in period after catheter placement, yet this period could be shortened with new insertion techniques.
Methods
We conducted a ...prospective cohort study to compare percutaneous vs. surgical catheter insertion in a newly established PD program. The break‐in period was intentionally shortened to <24 h to start PD almost immediately.
Results
We included 223 subjects who underwent percutaneous (34%) or surgical (66%) catheter placement. Compared to the surgical group, the percutaneous group had a higher proportion of early dialysis initiation within 24 h (97% vs. 8%, p < 0.001), similar successful initiation rates (87% vs. 92%, p = 0.34), and shorter lengths of stay (12 9–18 vs. 18 14–22 days, p < 0.001). Percutaneous insertion increased the likelihood of successful PD initiation within 24 h (OR 74, 95% CI 31–182), without increasing major complications.
Conclusion
Percutaneous placement could represent a cost‐effective and efficient technique to shorten break‐in periods.
There is considerable confusion about what ranges of dietary salta could be considered low, normal, or high and also what ranges of reduction in dietary salt are small or large. The World ...Hypertension League with other organizations involved in dietary salt reduction have proposed a standardized nomenclature based on normal ancestral levels of salt intake and also on ranges of reduction in salt intake in clinical and population interventions. Low daily salt (sodium) intake where harm due to deficiency would be expected to occur is recommended to remain undefined because of inadequate research but likely <0.25 g (100 mg), normal (physiological) intake <2.5 g (1000 mg), recommended intake <5.0 g (2000 mg), high ≥5.0 g (2000 mg), very high >10 to 15 g (4000–6000 mg), and extremely high >15 g (6000 mg). Reductions in daily salt (sodium) intake are recommended to be called small if <2.5 g (1000 mg), moderate if 2.5 to 5.0 g (1000–2000 mg) and large if >5.0 g (2000 mg). Use of this nomenclature is likely to result in less confusion about salt intake and interventions to reduce dietary sodium.
PDF
