Hepatocyte nuclear factor 4α mediated quinolinate phosphoribosylltransferase (QPRT) expression in the kidney facilitates resilience against acute kidney injury.

Nicotinamide adenine dinucleotide (NAD+) levels decline in experimental models of acute kidney injury (AKI). Attenuated enzymatic conversion of tryptophan to NAD+ in tubular epithelium may contribute to adverse cellular and physiological outcomes. Mechanisms underlying defense of tryptophan-dependent NAD+ production are incompletely understood.

Lactate-induced activation of HCA2 improves survival in mice with sepsis.

Sepsis is characterized by systemic inflammation that is caused by infection and by activation of proinflammatory pathways, resulting in mitochondrial and cellular dysfunction leading to multiorgan failure. Here, we show the following: ) in peritoneal immune cells, particularly macrophages, from mice that have undergone cecal ligation and puncture (CLP), hydroxycarboxylic acid receptor 2 (HCA2) expression increased in parallel with proinflammatory cytokines; ) post-CLP survival rates of knockout mice ( = 22) were lower than those of wild-type (WT) mice ( = 15) ( < 0.011), which is suggestive of a protective role for HCA2 in sepsis; ) WT mice subjected to CLP-induced sepsis and treated with lactated Ringer's solution (LR, = 13) survived longer than those treated with normal saline ( = 14; < 0.

De novo thrombotic microangiopathy after kidney transplantation.

Thrombotic microangiopathy (TMA) is a serious complication of transplantation that adversely affects kidney transplant recipient and allograft survival. Post-transplant TMA is usually classified into two categories: 1) recurrent TMA and 2) de novo TMA. Atypical hemolytic uremic syndrome (aHUS) resulting from dysregulation and over-activation of the alternate complement pathway is a rare disease but the most common diagnosis associated with recurrence in the allografts.

Mechanisms of gut microbiota-mediated bone remodeling.

The mechanisms underlying the systemic effects mediated by gut microbiota are under active investigation. In addition to local, direct effects of gut microbiota on the host, metabolic products from microbiota may act peripherally, reaching distal organs through the circulation. In our recent publication we demonstrated that gut microbiota influence bone remodeling distally, promoting both bone resorption and formation.

Uricosuric targets of tranilast.

Uric acid, generated from the metabolism of purines, has both proven and emerging roles in human disease. Serum uric acid in humans is determined by production and by the net balance of reabsorption and secretion in kidney and intestine. In the human kidney, epithelial reabsorption dominates over secretion, such that in normal subjects there is at least 90% net reabsorption of filtered urate resulting in a fractional excretion of <10%.

Insulin and SGK1 reduce the function of Na+/monocarboxylate transporter 1 (SMCT1/SLC5A8).

SMCTs move several important fuel molecules that are involved in lipid, carbohydrate, and amino acid metabolism, but their regulation has been poorly studied. Insulin controls the translocation of several solutes that are involved in energetic cellular metabolism, including glucose. We studied the effect of insulin on the function of human SMCT1 expressed in Xenopus oocytes.

The role of HCA2 (GPR109A) in regulating macrophage function.

We investigated the novel role of HCA2 (GPR109A) and its ligand nicotinic acid in regulating macrophage function. Hca2 expression in the RAW264.7 murine macrophage cell line is strongly induced by LPS treatment and correlates with the expression of TNF-α.

Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways.

Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited disorder mostly caused by mutations in PKD1, encoding polycystin-1 (PC1). The disease is characterized by development and growth of epithelium-lined cyst in both kidneys, often leading to renal failure. There is no specific treatment for this disease.

Ischemic injury enhances dendritic cell immunogenicity via TLR4 and NF-kappa B activation.

Ischemic (isc) injury during the course of transplantation enhances the immunogenicity of allografts and thus results in poorer graft outcome. Given the central role of dendritic cells (DCs) in mounting alloimmune responses, activation of donor DCs by ischemia may have a primary function in the increased immunogenicity of isc allografts. In this study, we sought to investigate the effect of ischemia on DC activity in vitro.

The independent association between serum uric acid and graft outcomes after kidney transplantation.

Background: Improving long-term outcomes of kidney transplantation depends on identifying novel risk factors that lead to poor outcomes. We sought to evaluate the predictive value of mean uric acid (UA) level during the first 6 months posttransplant for graft survival and function.

Methods: Two hundred twelve recipients of living donor kidneys transplanted during January 2000 to December 2001 were included.

Slc26a9 is inhibited by the R-region of the cystic fibrosis transmembrane conductance regulator via the STAS domain.

SLC26 proteins function as anion exchangers, channels, and sensors. Previous cellular studies have shown that Slc26a3 and Slc26a6 interact with the R-region of the cystic fibrosis transmembrane conductance regulator (CFTR), (R)CFTR, via the Slc26-STAS (sulfate transporter anti-sigma) domain, resulting in mutual transport activation. We recently showed that Slc26a9 has both nCl(-)-HCO(3)(-) exchanger and Cl(-) channel function.

Slc26a9--anion exchanger, channel and Na+ transporter.

The SLC26 gene family encodes anion transporters with diverse functional attributes: (a) anion exchanger, (b) anion sensor, and (c) anion conductance (likely channel). We have cloned and studied Slc26a9, a paralogue expressed mostly in lung and stomach. Immunohistochemistry shows that Slc26a9 is present at apical and intracellular membranes of lung and stomach epithelia.

Dopamine D1-like receptor-mediated inhibition of Cl/HCO3- exchanger activity in rat intestinal epithelial IEC-6 cells is regulated by G protein-coupled receptor kinase 6 (GRK 6).

The present study investigated the effect of dopamine D1-like receptor stimulation on the Cl-/HCO3- exchange activity in rat intestinal epithelial IEC-6 cells. The Cl-/HCO3- exchange activity was found to be a chloride-dependent, DIDS-sensitive and niflumate-insensitive process. The presence of the SLC26A6 anion exchanger was detected by both RT-PCR and immunoblotting analysis in IEC-6 cells, in which three different small interfering RNAs (siRNAs) targeting SLC26A6 markedly inhibited Cl-/HCO3- exchange.

Physiology of electrogenic SLC26 paralogues.

SLC26 anion exchangers transport monovalent and divalent anions, with a diversity of anion specificity and stoichiometry. Our microelectrode studies indicate that several SLC26 members are electrogenic. We reported that Slc26a6 functions as a Cl-/formate, Cl-/oxalate, Cl-/OH- and electrogenic Cl-/nHCO3- exchanger.

Renal urate transport.

Serum uric acid is determined by a balance between production and renal excretion. Luminal reabsorption of urate by the proximal tubule from the glomerular ultrafiltrate involves coupling between sodium-anion cotransport and urate-anion exchange. Apical sodium-coupled cotransport of lactate, ketoacids, nicotinate, and pyrazinoate increases intracellular levels of these anions in proximal tubular cells, stimulating the apical absorption of luminal urate via anion exchange.

Adult hypertension and kidney disease: the role of fetal programming.

Hypertension (HTN) and chronic kidney disease are highly prevalent diseases that tend to occur more frequently among disadvantaged populations, in whom prenatal care also tends to be poor. More and more evidence is emerging highlighting the important role of fetal programming in the development of adult disease, suggesting a possible common pathophysiologic denominator in the development of these disorders. Epidemiologic evidence accumulated over the past 2 decades has demonstrated an association between low birth weight and subsequent adult HTN, diabetes, and cardiovascular disease.

A C-terminal domain in KCC2 confers constitutive K+-Cl- cotransport.

The neuron-specific K(+)-Cl(-) cotransporter KCC2 plays a crucial role in determining intracellular chloride activity and thus the neuronal response to gamma-aminobutyric acid and glycine. Of the four KCCs, KCC2 is unique in mediating constitutive K(+)-Cl(-) cotransport under isotonic conditions; the other three KCCs are exclusively swelling-activated, with no isotonic activity. We have utilized a series of chimeric cDNAs to localize the determinant of isotonic transport in KCC2.

Primary and secondary prevention of chronic kidney disease.

The incidence and prevalence of chronic kidney disease (CKD) is on the rise worldwide. End-stage renal disease (ESRD) is the most advanced form of CKD, requiring some form of renal replacement therapy to ensure survival. Interventions to prevent or slow the progression of CKD, irrespective of the original cause, are thus of significant importance.

Acetaminophen-induced anion gap metabolic acidosis and 5-oxoprolinuria (pyroglutamic aciduria) acquired in hospital.

A rare cause of high anion gap acidosis is 5-oxoproline (pyroglutamic acid), an organic acid intermediate of the gamma-glutamyl cycle. Acetaminophen and several other drugs have been implicated in the development of transient 5-oxoprolinemia in adults. We report the case of a patient with lymphoma who was admitted for salvage chemotherapy.

Roles of Slc13a1 and Slc26a1 sulfate transporters of eel kidney in sulfate homeostasis and osmoregulation in freshwater.

Sulfate is required for proper cell growth and development of all organisms. We have shown that the renal sulfate transport system has dual roles in euryhaline eel, namely, maintenance of sulfate homeostasis and osmoregulation of body fluids. To clarify the physiological roles of sulfate transporters in teleost fish, we cloned orthologs of the mammalian renal sulfate transporters Slc13a1 (NaSi-1) and Slc26a1 (Sat-1) from eel (Anguilla japonica) and assessed their functional characteristics, tissue localization, and regulated expression.

Strategies to retard the progression of chronic kidney disease.

Chronic kidney disease (CKD) is a common and, in advanced cases, highly morbid disorder. The most severe form of CKD is end-stage renal disease (ESRD), in which the patient requires some form of renal replacement therapy to survive. The increasing incidence, prevalence, and costs of ESRD are major national health care concerns; interventions that may prevent or slow the progression of CKD towards ESRD are extremely important and the focus of this article.

Why is proteinuria an ominous biomarker of progressive kidney disease?

Progressive tubule injury and interstitial fibrosis frequently accompany glomerulopathies associated with proteinuria. Clinical experience indicates that higher levels of proteinuria prior to, as well as after initiation of treatment predict more rapid decline in renal function and more pronounced tubulointerstitial injury. It has been proposed that filtration of potentially tubulotoxic plasma proteins is responsible for the observed correlations between proteinuria and progression (i.

Diagnostic Investigation of Pyelonephritis.

Urinary tract infections are common, especially among women, and cause significant morbidity. While prognosis is probably more dependent on whether or not an episode of urinary tract infection is complicated (ie, associated with functional, metabolic, or anatomic abnormalities of the urinary tract) or uncomplicated, anatomic localization of infection has important implications for therapy. Pyelonephritis is difficult to diagnose with a high degree of accuracy based on clinical findings alone.