Welcome to Frontiers in Nephrology. In this issue of JASN, Frontiers in Nephrologyis inaugurated as a new regular feature that will appear every three to four months in future issues. As the new editorial team reviewed the mission of the journal, something became abundantly clear. In many areas of nephrology, we have become strategically positioned to truly translate advances in biomedical research all the way to the bedside and often back again to the bench to further unravel renal physiology and pathophysiology. The goal of Frontiers in Nephrologyis to highlight and feature certain topics of interest to nephrologists for which recent advances in basic science have relevance to clinical problems that we encounter in our patients, linking these reviews to an overview and update of one such disease entity. The goal is not only to use this forum to translate basic science for the clinicians but also to catalyze new questions and hypotheses that both clinical and basic science investigators may pursue. With Frontiers in Nephrology, we hope to merge the best of the other regular special features of JASN, Science Watch, Invited Reviews, and Disease of the Month, to focus on a single unifying disease or theme.
The first Frontiers in Nephrology, which appears in this issue and deals with the topic of renal tubular acidosis (RTA), illustrates our intent. The clinical entity of RTA was first described in 1935 and first ascribed to dysfunction of renal tubules in 1946. While familial forms of this syndrome have long been known to exist, it is only in recent years that the genetic basis of these entities has begun to be elucidated. Such experiments of nature provide a rare opportunity to study the function of single tubular transporters, co-transporters, ion exchangers, and enzymes in humans. Dr. Igarashi and his colleagues review proximal RTA, including recent studies that have identified mutations in the gene encoding the basolateral Na+/HCO3− co-transporter in patients with autosomal recessive proximal RTA, and discuss other candidates, including the gene encoding the apical membrane Na+/H+ exchanger isoform 3 as a possible cause of autosomal dominant proximal RTA. An interesting association—it appears that defects in sodium bicarbonate co-transport activity in ocular tissue also explain the eye abnormalities present in the autosomal recessive patients.
Dr. Karet reviews recent advances in the identification of genes expressed by α-intercalated cells that are responsible for inherited forms of distal RTA. Mutations in the basolateral anion exchanger AE1 have been identified in patients with autosomal dominant distal RTA and also in a few kindreds with autosomal recessive distal RTA. This gene also encodes the erythrocyte isoform of AE1, with mutations known to cause hereditary spherocytosis and ovalocytosis. The apical proton pump (H+-ATPase) consists of several subunits. Genetic mutations in two subunits have been identified in families with autosomal recessive RTA: genes encoding the B1 and a4 subunits. Normal function of this proton pump also appears to be important in the regulation of endolymph composition in the inner ear, which likely explains why most patients with mutant B1 subunits also develop progressive sensorineural hearing loss. Dr. Rodríguez-Soriano’s review of the clinical entity serves to emphasize the diversity of the clinical spectrum of RTA. Investigating alterations in the expression and function these genes in the more common acquired forms of RTA should provide interesting new insights into renal (and extrarenal) pathophysiology and potentially even novel therapeutics.
In an editorial accompanying this one, R. Curtis Morris, MD, whose team of clinical investigators at the University of California at San Francisco in the 1960s and 1970s, including Tony Sebastian and Elisabeth McSherry, performed so many of the seminal clinical studies that led to current understanding of the clinical subtypes of RTA that are now being characterized at the molecular level, provides a unique perspective on the evolution of this story from then to the present time.
Frontiers in Nephrology is off to a great start. Each subsequent installment will include the addition of a guest editor to assist us with the selection of topics and authors and to help with the peer review process in an effort to ensure that we remain on the cutting edge of recent advances. Already in preparation are Frontiers in Nephrology focusing on the glomerular podocyte, kidney development, diabetes, acute renal failure, and angiogenesis. The editorial team invites suggestions for future themes and welcomes your comments as we continue to advance on the research frontier.
- © 2002 American Society of Nephrology