Dysfunction of cellular transporters and predisposition to diabetic nephropathy.
Diabetic nephropathy is presently the first reason of end stage renal failure in Europe and the USA and its worldwide prevalence is rapidly increasing. Several studies have demonstrated that diabetes per se is not sufficient to induce nephropathy and a genetic predisposition has to be present as well. Looking for genetic markers, investigators have been helped by the finding that a predisposition to hypertension facilitates the development of nephropathy in diabetic patients. Prompted by the evidence that essential hypertension is characterized by a number of defects at cellular level, similar dysfunctions have been searched also in cells obtained from diabetic patients with nephropathy. Increased Na-Li countertransport and Na-H exchange activities, slower Ca pump and faster cell proliferation rate have been found in cells obtained from patients affected by diabetic nephropathy. The definition of these intermediate phenotypes represents a necessary step toward the identification of the molecular dysfunction(s) underlying the development of diabetic nephropathy. The present review will focus on the description of the different cell dysfunctions identified in patients affected by diabetic nephropathy, their pathophysiologic meaning and will try to define an unifying hypothesis that, by linking together the different dysfunctions, will highlight a few areas "at risk", candidate to home the primitive genetic abnormality.
Zerbini
Gianpaolo
G
Renal Pathophysiology Laboratory, Division of Medicine, San Raffaele Scientific Institute, Milan I-20132, Italy. g.zerbini@hsr.it
Gabellini
Daniela
D
Ruggieri
Dora
D
Maestroni
Anna
A
D017920:Antiporters / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D002462:Cell Membrane / Q000502:physiology; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D017920:Antiporters; D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; C045885:sodium-lithium countertransporter; D002118:Calcium