Brain dysfunction in tubular and tubulointerstitial kidney diseases

Abstract

Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a reduced GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue, we have selected a group of primary tubular diseases with preserved GFR, in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory, and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen as examples to highlight this topic, Bartter and Gitelman syndromes and nephrogenic diabetes insipidus. We discuss current published findings, some unanswered questions, and propose topics for future research.

Wall Tension and Tubular Resistance in Kidney Cystic Conditions

“… Brain: No gross brain abnormalities have been described in patients with ADPKD. However, they might suffer from depression [ 67 ]. Interestingly, no mild cognitive impairment has been reported in these patients, although it is often present in other forms of CKD [ 67 , 68 , 69 , 70 , 71 , 72 , 73 ].…”

“…However, they might suffer from depression [ 67 ]. Interestingly, no mild cognitive impairment has been reported in these patients, although it is often present in other forms of CKD [ 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. Both PKD1 and PKD2 have large expression in the brain (data from Allen Brain Atlas database and from Human Protein Atlas database).…”

Construction and Evaluation of a Novel Organic Anion Transporter 1/3 CRISPR/Cas9 Double-Knockout Rat Model

“…The majority of endogenous metabolites and exogenous compounds are excreted from the body by the kidney, which is the net result of glomerular filtration, tubular secretion and reabsorption [1,2]. There are multiple transporters involved in tubular secretion, including organic anion transporters (OATs) and organic cation transporters (OCTs) [3,4], of which OAT1 and OAT3 are largely responsible for the renal uptake of organic anionic drugs and a few organic cationic drugs from the blood, and thus may be the major rate-limiting steps in the renal elimination of these drugs [5][6][7][8].…”