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Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness. [ABSTRACT FROM AUTHOR]

Background: Ferric citrate (FC) is a new phosphorus binder shown to increase serum iron stores while reducing intravenous iron and erythropoiesis-stimulating agent usage. Such reductions could lower hospitalization rates and associated costs. Methods: Hospitalizations during a Phase III trial were compared between FC and active control (AC). Hospitalization costs were estimated using the 2013 US Renal Data System Annual Data Report. Results: 34.6% of FC patients were hospitalized at least once versus 45.6% of the AC group (risk reduction 24.2%; p = 0.02). There were 181 unique hospitalizations in the FC group versus 239 in the AC group, for a difference of 58 hospitalizations. Total potential savings was US$ 867,622 in hospitalization costs in the FC group. If the hospitalization reduction in our study was applied to the general end-stage renal disease population, this could translate into a savings of US$ 3002/patient/year. Conclusions: Patients receiving FC experienced fewer hospitalizations with the potential for significant savings. [ABSTRACT FROM AUTHOR]

From 88 subjects with labile high blood pressure (LHBP), we collected blood pressure variability (BPV) and assessed relationships with age, medications, and nocturnal pattern via ambulatory blood pressure monitoring. The average age of the subjects was 64 ± 13 years and they were on 1.5 ± 1.3 antihypertensives. BPV did not differ diurnally and was not influenced by medication. Aging associates with increasing daytime systolic but not diastolic BPV, with increasing nighttime systolic BP, and decreasing diastolic BP diurnally. Subjects had widened pulse pressure and abnormal diurnal pattern with age. Further studies are needed to stratify an individual's risk associated with LHBP. [ABSTRACT FROM AUTHOR]

We describe a 61-year-old woman with acute kidney injury, nephrotic range proteinuria and hematuria. Kidney biopsy showed membranous glomerulopathy (MG) with superimposed pauci-immune necrotizing crescentic glomerulonephritis (PNCGN). Coexistent MG and PNCGN is a rare occurrence. The diagnosis of such an exceptionally rare combination relies on the combination of renal biopsy findings and serologic testing. We also review previous reported cases and discuss possible pathogenesis of this rare dual glomerulopathy. [ABSTRACT FROM AUTHOR]

Type 2 diabetic nephropathy (type 2 DN) patients traditionally develop significant proteinuria prior to the development of renal impairment. However, this clinical paradigm, based on observations prior to the widespread usage of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), has recently been questioned. 2,303 patients enrolled in the Sulodexide Overt Nephropathy Study (OVERT) were analyzed. Prior therapy with ACEi and/or ARB at the time of screening was recorded in 951 patients. 22% of patients had significant renal impairment with a PCR at screening of <500 mg/g. Therapy with ACEi and/or ARB at the time of screening was recorded in 94%, where prior medication data was available. In patients with type 2 DN and advanced renal impairment, levels of proteinuria below that which traditionally defines overt diabetic nephropathy, are found in more than one fifth of patients. We suggest that the high prevalence of ACEi and ARB usage in patients with type 2 DN may be effecting the traditional clinical paradigm of type 2 DN. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to assess the validity of the RT3 accelerometer, and its inbuilt algorithm, in measuring inactivity, walking and running in children. Twenty children, aged 7–12 years, participated in the study. The RT3 was compared to physiological energy expenditure obtained via a wireless portable ergospirometric system. Data analysis was performed using Bland and Altman plots and Pearson product moment correlation coefficients. There were no significant differences between the methods for each activity. Bland and Altman 95% limits of agreement between the two measures in kcalmin−1 for each of the activities were as follows: inactivity (−0.058, 0.47), walking at 3kmh−1 (−1.22, 0.83) brisk walking at 6kmh−1 (−2.74, 0.54), brisk walking at 6kmh−1 on an incline of a 10% gradient (−1.69, 2.11), and jogging at 9kmh−1 (−3.67, 1.24). Energy expenditure via the RT3 correlated significantly with that obtained by indirect calorimetry for each activity independently (r =0.56–0.84, all P <0.01). The RT3 provided a valid estimate of inactivity, walking and running and would thus appear appropriate for the objective measurement of physical activity levels. [Copyright &y& Elsevier]

Introduction: Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial., Methods: Patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m 2 and urinary albumin-to-creatinine ratio (UACR) 200-5,000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR., Results: Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. The mean (SD) age was 59.9 ± 12.1 years, the mean eGFR was 45.7 ± 12.1 mL/min/1.73 m 2 , and the median UACR was 1,694.5 (25%, 75% range 891-2,582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were -3.87 and -4.29 and -2.66 and -4.22 mL/min/1.73 m 2 /year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73 m 2 /year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (-29.3% ± 1.2% vs. -3.6% ± 1.1%; between-group mean difference [95% CI] -26.7 [-50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event., Conclusion: In membranous nephropathy, the effects of dapagliflozin on kidney disease progression and albuminuria were generally favorable; there was insufficient power to justify formal inference testing., Competing Interests: G.M.C. served on the Executive Committee of the DAPA-CKD trial. He has served on the Board of Directors of Satellite Healthcare, a non-profit dialysis provider. He has served as Chair or Co-Chair of Trial Steering Committees with Akebia, CSL Behring, Sanifit, and Vertex. He has served as an Advisor to Applaud, Ardelyx, Calico, CloudCath, Durect, Eliaz Therapeutics, Miromatrix, Outset, Renibus, and Unicycive. He has served on Data Safety Monitoring Boards with Bayer, Mineralys, and ReCor. H.J.L.H. reported receiving research support from and serving as a consultant for AstraZeneca during the conduct of the study; serving as a consultant for Bayer, Chinook Tx, CSL Behring, Dimerix, Eli Lilly, Fresenius, Gilead, Novartis, and Travere Therapeutics outside the submitted work; receiving grants and research support from Boehringer Ingelheim and Janssen outside the submitted work; and receiving grants and clinical trial study medication from, and serving as a consultant for Novo Nordisk outside the submitted work. P.B.M. reported receiving lecture fees and travel to meetings support from Vifor, AstraZeneca, Pharmacosmos, Napp, Astellas, lecture fees from Novartis, Astellas, GSK and grants from Boehringer Ingelheim outside the submitted work. J.P.D. reported receiving fees from AstraZeneca for the conduct of this study; fees from Sanofi-Aventis and CSL Behring as part of a steering committee; fees from Novo Nordisk for outcome adjudication for a trial; fees from Goldfinch Bio, Birdrock Bio, and Boehringer Ingelheim for study design; personal fees from Bayer. M.N. reported receiving honoraria from Boehringer Ingelheim, Swixx Biopharma, Roche, Sanofi Genzyme and Omeros. D.C.W. reported receiving personal fees from AstraZeneca during the conduct of the study; personal fees from Astellas, Boehringer Ingelheim, Bayer, GlaxoSmithKline, Janssen, Gilead, Merck Sharp and Dohme, George Clinical, Intas, ProKidney, Tricida, Vifor, and Zydus outside the submitted work; and performing guideline development for KDIGO. R.C.-R. reported receiving personal fees from AstraZeneca, during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Amgen, personal fees from Janssen, grants from GlaxoSmithKline, grants and personal fees from Novo Nordisk, personal fees from Medtronic, outside the submitted work. P.R. reported receiving grants and other from AstraZeneca, during the conduct of the study; from Novo Nordisk, Gilead, Bayer, Sanofi-Aventis, and Eli Lilly, outside the submitted work. R.D.T.’s contribution to this manuscript was supported in part by endowments from the Mary M. Conroy Professorship in Kidney Diseases and the Houston J and Florence A Dosswell Center for Development of New Approaches for the Treatment of Hypertension. He also reported receiving personal fees from AstraZeneca, during the conduct of the study; personal fees from AstraZeneca, Bayer Pharma, Calliditas, Boehringer Ingelheim, Relypsa, Amgen, and Novartis, outside the submitted work. A.M.L. reported being a full-time employee and shareholder of AstraZeneca during the conduct of the study. N.J. reports travel grants from AstraZeneca., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Iron stores assuring optimal efficacy/safety for erythropoiesis are unknown in the dialysis population. Using multicenter trial data, we related safety profiles, erythropoiesis-stimulating agent (ESA), and intravenous iron dosing to achieved iron stores in 441 subjects randomized 2 : 1 to ferric citrate or active control as their phosphate binder over 52 weeks. Intravenous iron was given at each site's discretion if ferritin ≤ 1,000 ng/mL and transferrin saturation ≤ 30%. Multivariable time-dependent Cox regression jointly related the primary safety outcome (composite of cardiac, infection, gastrointestinal, and hepatobiliary serious adverse events) to moving averages of ferritin and transferrin saturation over the preceding 90 days with covariate adjustment. Multivariable generalized estimating equations related elevated ESA and intravenous iron doses to trailing 90-day averages of ferritin and transferrin saturation with covariate adjustment. The adjusted hazard ratio for the safety composite per 10% increase in transferrin saturation was 0.84 (95% confidence interval 0.68 - 1.02, p = 0.08) and 1.09 (0.86 - 1.35, p = 0.48) per 400 ng/mL increase in ferritin. The adjusted hazard ratio for the safety composite was 0.50 (0.29 - 0.88, p = 0.016) for the highest transferrin saturation tertile vs. the lowest. Adjusted odds ratios for higher intravenous iron dose were lower in the highest (0.23 [0.16 - 0.35], p < 0.001) and middle transferrin saturation tertile (0.42 [0.31 - 0.57], p < 0.001) vs. lowest. Incidence of elevated ESA dose was lower in the highest transferrin saturation tertile (p = 0.01). Ferritin did not predict clinical events or ESA dose. Transferrin saturation may be a better marker than serum ferritin to judge optimal iron stores in dialysis patients. Transferrin saturations > 34% are safe and provide maximal efficacy.
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Objective: The purpose of our study was to evaluate the prevalence of nephrogenic systemic fibrosis (NSF) and nephrotoxicity among patients with differing degrees of renal dysfunction who are exposed to high doses of gadodiamide., Materials and Methods: A search of medical records identified patients who received high-dose IV gadodiamide for catheter angiography or CT between January 2002 and December 2005. The cohort was limited to patients who had received a dose of at least 40 mL of gadodiamide during a single imaging session, who underwent at least 1 year of clinical follow-up, and who had moderate to end-stage renal disease (estimated glomerular filtration rate [GFR] < 60 mL/min/1.73 m(2)) established within the previous 48 hours. Any observation suggestive of NSF was recorded, as were all estimated GFR values obtained during the 2 weeks before and the 5 days after gadodiamide administration., Results: Sixty-one patients met the inclusion criteria. The median estimated GFR was 30 mL/min/1.73 m(2) (range, 3-57 mL/min/1.73 m(2)). The median gadodiamide exposure was 80 mL (range, 40-200 mL). NSF eventually developed in one of the 61 patients, yielding a prevalence of 1.6%. Among the 33 patients not undergoing dialysis with estimated GFR documented within 5 days after contrast injection, the change in estimated GFR ranged from -8.8 to 42.9 mL/min/1.73 m(2), with a statistically significant median improvement of 2.4 mL/min/1.73 m(2) (p = 0.007)., Conclusion: Although gadolinium exposure appears to be a necessary precondition for NSF, gadolinium-based contrast agents alone are not sufficient to cause the disorder, even in very high doses. Clinically relevant nephrotoxicity of gadolinium-based contrast agents was not found.