This Month's Highlights

doi:10.1681/ASN.2009010095

BRIEF COMMUNICATION

Proximal Tubule Responsible for Albuminuria

Many studies have assigned blame for albuminuria in diabetic nephropathy to alterations of the glomerular filtration barrier. Russo et al. challenge this paradigm by using intravital microscopy to follow the handling of labeled albumin or dextran by normal and diabetic kidneys. In an animal model of diabetes, they demonstrate that the onset of albuminuria does not occur because of changes in glomerular permeability but rather because of reduced reabsorption of albumin by the proximal tubule. Furthermore, excretion of albumin-derived peptides precedes albuminuria, suggesting that peptiduria may be clinically useful for the early detection of diabetic nephropathy. See Russo et al., pages 489–494.

BASIC RESEARCH

Soluble Thrombomodulin Benefits Ischemic AKI

Endothelial dysfunction and other disturbances to the renal microvasculature contribute to the damage that accompanies ischemic acute kidney injury (AKI). Downregulation of thrombomodulin (TM), a glycoprotein on endothelial cell membranes, may contribute to the procoagulable state of the microvasculature after ischemia. In this issue, Molitoris et al. show that administration of soluble TM in a mouse model of ischemic AKI attenuates renal dysfunction and histologic injury and improves microvascular function. These data suggest a possible therapeutic use for soluble TM for ischemic AKI. See Sharfuddin et al., pages 524–534.

C3a Mediates Tubulointerstitial Injury

In proteinuric states, proteins in the glomerular filtrate may contribute to tubulointerstitial injury. Proteins of the complement system are filtered, and activation of this system generates the proinflammatory anaphylotoxins C3a and C5a. In this issue, Tang et al. report that C3a induces epithelial-to-mesenchymal transition of tubular epithelial cells in vitro. Furthermore, mice lacking the C3a receptor are protected from renal injury in the setting of adriamycin-induced proteinuria. These data support an important role for C3a in tubulointerstitial injury. See Tang et al., pages 593–603.

CLINICAL RESEARCH

Chewing Away at Hyperphosphatemia

Have you ever considered the phosphate content of saliva? We ingest 500 to 700 ml of saliva daily, and patients with chronic kidney disease have high concentrations of salivary phosphate. Savica et al. hypothesized that binding salivary phosphate between meals could improve control of hyperphosphatemia among patients on hemodialysis. They developed a phosphate-binding chewing gum and demonstrated a 31% reduction in serum phosphate when patients chewed the gum twice daily for 2 wk in addition to the continued use of phosphate binders at meals. These results suggest that targeting salivary phosphate may be a useful approach to treat hyperphosphatemia. See Savica et al., pages 639–644.

High-Flux Membranes Help the Hypoalbuminemic

The HEMO study did not detect a significant overall survival advantage between high-flux and low-flux dialysis membranes among prevalent hemodialysis patients, but whether high-flux membranes could benefit patients with specific characteristics remains unknown. Here, Locatelli et al. report the results of a randomized, controlled trial that assigned >700 incident hemodialysis patients to high-flux or low-flux dialysis membranes, stratified by serum albumin above or below 4 g/dl. Similar to HEMO, there was no significant survival difference overall between membrane types. The survival rates in the high-flux group were greater, however, for patients with albumin <4 g/dl or diabetes. These results suggest that high-flux membranes may confer survival benefit to specific patient groups. See Locatelli et al., pages 645–654.

Redefining Acute Kidney Injury

Acute kidney injury (AKI) has been defined by either absolute or percentage changes in serum creatinine. Waikar and Bonventre investigated the implications of these varying definitions by modeling creatinine kinetics in the setting of AKI. They found that the percentage change of serum creatinine after AKI depends highly on baseline kidney function, whereas the absolute change of serum creatinine is nearly identical across different levels of baseline kidney function. On the basis of their models, the authors propose a definition of AKI based on absolute changes of serum creatinine during a 24- to 48-h period. See Waikar and Bonventre, pages 672–679.