Linda H Ficociello,1 Joanna Willetts,1 Claudy Mullon,1 Curtis Johnson,2 Michael S Anger,1 Jeffrey L Hymes1 1Global Medical Office, Fresenius Medical Care, Waltham, MS, USA; 2Spectra Laboratories, ...Southaven, MS, USA Correspondence: Jeffrey L Hymes, Fresenius Medical Care, 1000 Corporate Centre Drive, Suite 400, Franklin, TN, 37067, USA, Email email protected
Regression of Microalbuminuria in Type 1 Diabetes Perkins, Bruce A; Ficociello, Linda H; Silva, Kristen H ...
The New England journal of medicine,
06/2003, Letnik:
348, Številka:
23
Journal Article
Recenzirano
Odprti dostop
Microalbuminuria in type 1 diabetes has been thought to herald an inexorable process leading to overt proteinuria and progressive nephropathy. In this study of patients who had persistent ...microalbuminuria during an initial two-year evaluation period, 58 percent had regression of their microalbuminuria during the subsequent six years.
Elevated albumin excretion may not lead to progressive nephropathy.
In the early 1980s, three landmark studies of patients with type 1 diabetes suggested an ominous prognosis for those with minute elevations of urinary albumin excretion, designated as microalbuminuria. Microalbuminuria was said to confer a 60 to 85 percent risk of the development of overt proteinuria within 6 to 14 years.
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Although derived from small studies, this model of diabetic nephropathy held that microalbuminuria in type 1 diabetes heralded an inexorable process leading to overt proteinuria.
Other prospective studies challenged this model, suggesting a considerably lower risk of progression to proteinuria
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; in some patients microalbuminuria remained stable, . . .
Hypoalbuminemia results when compensatory mechanisms are unable to keep pace with derangements in catabolism/loss and/or decreased synthesis of albumin. Across many disease states, including chronic ...kidney disease (CKD), hypoalbuminemia is a well-established, independent risk factor for adverse outcomes, including mortality. In the setting of CKD, reduced serum albumin concentrations are often a manifestation of protein-energy wasting, a state of metabolic and nutritional alterations resulting in reduced protein and energy stores. The progression of CKD to kidney failure and the initiation of maintenance hemodialysis (HD) further predisposes an already at-risk population toward hypoalbuminemia such that approximately 60% of HD patients have albumin concentrations <4.0 g/dl. Albumin loss into the dialysate through the dialyzer appears to be a potentially modifiable cause of hypoalbuminemia in some patients. A group of newer dialyzers for maintenance HD-sometimes termed protein-leaking or medium cut-off membranes-aim to improve clearance of middle molecules (vs high flux dialyzers) but are associated with increased albumin losses. In this article, we will examine the impact of dialyzer selection on albumin losses during conventional HD, including the clinical relevance of such losses on serum albumin levels. Data on the clinical relevance of albumin losses during dialysis and current gaps in the evidence base are also discussed.
Phosphate binders are widely used to achieve serum phosphorus control in patients with end-stage renal disease. However, the large pill burden associated with these medications may decrease adherence ...to therapy. In clinical trials, sucroferric oxyhydroxide (SO) demonstrated equivalent control of serum phosphorus to sevelamer, with a lower daily pill burden. We examined changes in phosphate binder pill burden, medication possession ratio (MPR), and phosphorus control among in-center hemodialysis (ICHD) patients converting to SO from another phosphate binder as part of routine care.
Patients included in this retrospective analysis (N=490) were ≥18 years old, received ICHD at a large dialysis organization (LDO), and were enrolled in the LDO's pharmacy service. Patients converting to SO were those who had supply of another phosphate binder, received a first prescription fill for SO, and subsequently did not refill the non-SO phosphate binder. Patients were followed over the 6 months before and 6 months following the first SO fill and were censored from the analysis upon modality change, loss to follow-up, discontinuation of SO, or fill of a prescription for another phosphate binder after SO initiation (number censored=361). Outcome measures assessed were total phosphate binder pill burden and MPR, serum phosphorus, and percentage of patients with serum phosphorus ≤5.5 mg/dL.
Among patients converting to SO, mean phosphate binder pill burden was 10.8 pills/day during baseline; this decreased to 5.5 pills/day during follow-up (
<0.001). The percentage of patients with serum phosphorus ≤5.5 mg/dL increased from 22.0% to 30.0% (
<0.001). Among patients not using the LDO pharmacy's automated refill management service (N=30), mean phosphate binder MPR increased from 0.68 during baseline to 0.80 during follow-up (
=0.01).
In a cohort of ICHD patients, conversion to SO was associated with a reduction in pill burden, better adherence, and improvements in phosphorus control.
In prior analyses of real-world cohorts of hemodialysis patients switched from one phosphate binder (PB) to sucroferric oxyhydroxide (SO), SO therapy has been associated with improvements in serum ...phosphorus (sP) and reductions in daily PB pill burden. To characterize how SO initiation patterns have changed over time, we examined the long-term effectiveness of SO in a contemporary (2018-2019) cohort.
Adult Fresenius Kidney Care hemodialysis patients first prescribed SO monotherapy as part of routine care between May 2018 and May 2019 (N = 1792) were followed for 1 year. All patients received a non-SO PB during a 91-day baseline period before SO prescription. Mean PB pills/day and laboratory parameters were compared before and during SO treatment. Results were divided into consecutive 91-day intervals (Q1-Q4) and analyzed using linear mixed-effects regression and Cochran's Q test. These results were contrasted with findings from a historical (2014-2015) cohort (N = 530).
The proportion of patients achieving sP ≤5.5 mg/dl increased after switching to SO (from 27.0% at baseline to 37.8%, 45.1%, 44.7%, and 44.0% at Q1, Q2, Q3, and Q4, respectively;
< 0.0001 for all). The mean daily PB pill burden decreased from a baseline of 7.7 to 4.4, 4.6, 4.8, and 4.9, respectively, across quarters (
< 0.0001 for all). Patients in the contemporary cohort had improved sP control (27.0% achieving sP ≤5.5 mg/dl vs 17.7%) and lower daily PB pill burden (mean 7.7 vs 8.5 pills/day) at baseline than those in the historical cohort. Overall use of active vitamin D was similar between cohorts, although higher use of oral active vitamin D (63.9% vs 15.7%) and lower use of IV active vitamin D lower (23.4% vs 74.2%) was observed in the contemporary cohort.
Despite evolving treatment patterns, switching to SO resulted in improved sP control with fewer pills per day in this contemporary hemodialysis cohort.
It has been proposed that substituting citrate-acidified dialysate (CAD) solutions for acetate-acidified dialysate (AAD) could improve hemodynamics and dialysis tolerance and reduce the requirement ...for systemic anticoagulation. Citrate chelates ionized calcium, but long-term effects of CAD use during maintenance hemodialysis have not been well studied. While many studies of the effects of CAD on serum calcium and intact parathyroid hormone (iPTH) have been short-term or have been limited by sample size, we aimed to determine if there are any long-term (i.e., 6-month) changes from pre-dialysis iPTH levels when patients are switched from AAD to CAD.
This retrospective cohort study compared various clinical parameters, including pre-dialysis iPTH and serum calcium as well as single pool Kt/V, from eligible patients who received in-center hemodialysis thrice-weekly in geographically matched CAD (n=3) or AAD clinics (n=12). CAD clinics were defined as clinics converting from AAD to CAD if >85% of the patients were prescribed CAD after implementation of CAD within the clinic.
Pre-dialysis iPTH was not significantly different from baseline to 6-month follow-up within either CAD or AAD clinics. Moreover, the mean change from baseline to month 6 in iPTH between patients (n=142) in CAD clinics (-17 pg/mL) and patients (n=671) in AAD clinics (13 pg/mL) was similar (
= 0.24). Likewise, the differences in the mean change in serum calcium concentrations and dialysis adequacy (single pool Kt/V) were not significant between CAD and AAD clinics. For subgroups of patients who were never prescribed cinacalcet or calcium-based phosphate binders, there were no significantly different categorical shifts in iPTH between CAD and AAD clinics.
Similar trends in single pool Kt/V, iPTH, and serum calcium levels were observed in clinics that switched from AAD to CAD versus the geographically matched AAD clinics. These results support CAD as a potential alternative to AAD in hemodialysis.
Activin, a member of the TGFβ family of cytokines, signals through heteromeric transmembrane complexes composed of type I and type II Ser/Thr kinase receptors. Activated by type II receptors, the ...type I receptor phosphorylates, thereby activating its effectors Smad2 and Smad3. It has been shown that the ligand-bound TGFβ receptors endocytose to early endosomes, where they phosphorylate Smads. However, whether TGFβ and activin can signal without receptor internalization is still in question. We report that a mutation changing Trp477 to Ala in the kinase domain rendered the type I activin receptor Alk4 unable to undergo ligand-dependent internalization. However, the resultant receptor, named Alk4W477A, retained the ability to phosphorylate Smad2 and mediate activin-induced transcription activation. Also, a Trp477 to Ala mutation abolished the endocytosis of Alk4T206D, a constitutively active type I activin receptor. The action of the mutant Alk4T206D became activin dependent. Finally, blocking endocytosis by depletion of intracellular potassium did not inhibit Smad2 phosphorylation by Alk4W477A. Taken together, our data indicate that activin receptors can transduce activin signals without endocytosis and suggest the possibility that an endocytosis-independent activin signaling pathway exists, which may act as an alternative mechanism for signal transduction.
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