Review and discussion of tubular biomarkers in the diagnosis and management of diabetic nephropathy.

The prevalence of diabetic nephropathy has tremendously increased with the relentless rise in the incidence of diabetes over the last couple decades. Diabetic nephropathy is a leading cause of morbidity and mortality, and it invariably leads to an end-stage renal disease (ESRD). In an effort to delay the onset of ESRD systematic screening and appropriate management are needed to evaluate the progression of renal damage in diabetic nephropathy.

Creatinine clearance, cystatin C, beta2-microglobulin and TATI as markers of renal function in patients with proteinuria.

Background: Proteinuria is a risk factor for end-stage renal disease (ESRD). Creatinine clearance (CrCl) is usually used as a marker to monitor the progression of ESRD, while cystatin C (CYST) has also been considered as a marker of renal function. Tumor-associated trypsin inhibitor (TATI) has been shown to be a promising marker of renal function.

Tubular biomarkers to assess progression of diabetic nephropathy.

Despite aggressive management, many patients with diabetic nephropathy still develop end-stage renal disease. Accompanying tubulointerstitial damage is important in the progression of diabetic nephropathy. Markers of tubular damage, such as NGAL, KIM-1, and LFABP, have been proposed for monitoring the effectiveness of therapy.

Effects of Devil's Claw (Harpagophytum procumbens) on the multidrug transporter ABCB1/P-glycoprotein.

Unlabelled: Devil's Claw (Harpagophytum procumbens) a plant native to Southern Africa, has historically been used in traditional medicine to treat a wide range of diseases and currently is widely employed as anti-inflammatory and pain-relieving natural remedy in Europe and other parts of the world.

Aim Of The Study: Little is known about possible herb-drug interactions arising from effects of Devil's Claw on the major drug metabolizing enzymes or transporters. This study evaluated in vitro the effects of Devil's Claw on the multidrug transporter ABCB1/P-glycoprotein.

Albumin influences expression and function of the membrane transporter P-glycoprotein in HK-2 human proximal tubular cells.

Background: In proximal tubular cells exposed to albumin genes encoding membrane transporters were found to be up-regulated or down-regulated. P-glyco-protein (Pgp) is an efflux pump which transports a variety of compounds outside the cell. In the kidney, Pgp is located mainly on the luminal side of proximal tubular cells.

Simvastatin and fluvastatin reduce interleukin-6 and interleukin-8 lipopolysaccharide (LPS) stimulated production by isolated human monocytes from chronic kidney disease patients.

Background: Statins reduce lipid levels, inflammation and cardiovascular events in patients with coronary artery disease; CKD patients show increased risk of cardiovascular and increased plasma levels of IL-6 and IL-8.

Aim: To evaluate the in vitro effect of simvastatin (S) or fluvastatin (F) on the lipopolysaccharide (LPS) stimulated secretion of IL-6 and IL-8 from monocytes of chronic kidney disease patients (CKD) in K-DOQI stages 3-5.

Methods And Subjects: Monocytes enriched peripheral blood (PBMC) from 28 CKD (15 in K-DOQI stages 3-4, Group I, and 13 in K-DOQI stage 5 on hemodialysis, Group II) and 10 healthy subjects (HS), were isolated by Ficoll-gradient centrifugation.

Expression and functional characteristics of tubular transporters: P-glycoprotein, PEPT1, and PEPT2 in renal mass reduction and diabetes.

Renal mass reduction is associated with a compromise in renal excretion, and thus dosages of drugs need to be adjusted to avoid adverse reactions and to ensure their effectiveness. A prototypic example is patients who had undergone transplantation due to a variety of causes, including diabetic nephropathy; the latter appears to be the major cause of renal failure requiring hemodialysis and transplantation. Conceivably, hyperglycemia with reduced renal mass interferes in the delivery of xenobiotics handled by various tubular transporters.

In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients.

Background: The beneficial effects of statins in reducing cardiovascular events have been attributed predominantly to their lipid-lowering effects, recent studies suggest that these effects might be due to their anti-inflammatory properties. We here investigate the in vivo and in vitro effects of simvastatin on cytokine production in pre-dialysis chronic renal failure patients.

Methods: Our clinical study has been designed as a randomized double-blind placebo controlled study.

Matrix metalloproteinases in renal development.

Matrix metalloproteinases (MMPs) are enzymes with metal ion-dependent activity that degrade extracellular matrix (ECM) glycoproteins. MMPs play a vital role in various biological processes, such as embryogenesis, tissue remodeling, angiogenesis, and wound healing, and in certain disease processes, for example, metastasis of cancer cells. Following their activation, MMPs are believed to modulate both cell-cell and cell-matrix interactions, which in turn regulate cellular differentiation, migration, proliferation, and cell survival.

Effects of grapefruit juice on the multidrug transporter P-glycoprotein in the human proximal tubular cell line HK-2.

The multidrug transporter MDR-1 P-glycoprotein (Pgp) has been recently pointed out as an important mechanism underlying chemical interaction between drugs and many commonly ingested substances, including grapefruit juice (GFJ). Modulation of intestinal Pgp dependent transport by GFJ may lead to changes in bioavailability of drugs that are substrates of Pgp itself, by affecting their presystemic clearance. Since other cellular sites expressing Pgp and devoted to drug disposition, like kidney proximal tubules, could be involved in these pharmacokinetic interactions, we investigated the effect of GFJ on the expression and activity of Pgp in the human immortalized tubular cell line HK-2.

Assessment of tumor-associated trypsin inhibitor (TATI) as a marker of renal function.

Background: Low molecular weight (LMW) proteins have been proposed for renal function assessment. This study aimed to ascertain the usefulness of tumor-associated trypsin inhibitor (TATI), a LMW protein (6.200 d), as a glomerular filtration rate (GFR) marker.

Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line.

P-glycoprotein (Pgp), the MDR-encoded membrane transporter, is physiologically expressed in normal tissues with excretory functions, including kidney proximal tubules. In a preliminary report we have shown that HK-2, an immortalized cell line from normal human proximal tubule, expresses a functional Pgp and may be considered a valuable model for in vitro investigations on the Pgp role(s) in human renal pathophysiology. The present investigation was designed to further characterize the properties of HK-2 Pgp by exploring its responsiveness to a variety of exogenous or endogenous modulators.