Article

Glomerular expression of kidney injury molecule-1 and podocytopenia in diabetic glomerulopathy

Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
American Journal of Nephrology (Impact Factor: 2.65). 08/2011; 34(3):268-80. DOI: 10.1159/000330187
Source: PubMed

ABSTRACT Studies have shown that kidney injury molecule-1 (KIM-1) is upregulated in damaged renal proximal tubules. In this study, we examined KIM-1 expression in glomerular epithelial cells in diabetic glomerulopathy.
Renal histology, immunostaining and Western blot for protein level, and real-time PCR for mRNA expression of KIM-1 and podocyte markers were evaluated in untreated or losartan-treated Zucker lean (Fa/+) and Zucker diabetic fatty (Fa/Fa) rats.
The diabetic rats showed an increased glomerular expression of KIM-1. KIM-1 staining was localized primarily in the hyperplastic parietal epithelium of Bowman's capsule in the early stages of diabetes with subsequent increase in KIM-1-positive cells in the glomerular tuft in the more advanced stages. The increase in glomerular KIM-1 was associated with a decrease in podocytes in Fa/Fa rats. Antiproteinuric treatment with losartan attenuated podocytopenia and decreased renal expression of KIM-1 in treated diabetic rats. In an in vitro study, albumin overload increased KIM-1 protein in the primary cultures of rat glomerular epithelial cells.
These results show that glomerular KIM-1 expression was increased, in proportion to the extent of proteinuria and podocytopenia in the diabetic animals, supporting that KIM-1 could be used as a potential biomarker for glomerular injury in proteinuric kidney disease.

Download full-text

Full-text

Available from: John D Imig, Dec 21, 2013
0 Followers
 · 
152 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, it has become apparent that parietal epithelial cells (PECs) play an important role within the renal glomerulus, in particular in diseased conditions. In this review, we examine current knowledge about the role of PECs and their interactions with podocytes in development and under physiological conditions. A particular focus is on the crucial role of PECs and podocytes in two major glomerular disease entities. In rapidly progressive glomerulonephritis, PECs and podocytes proliferate and obstruct the tubular outlet, resulting in loss of the affected nephron. In focal and segmental glomerulosclerosis, PECs become activated and invade a segment of the glomerular tuft via an adhesion. From this entry site, activated PECs displace podocytes and deposit matrix. Thus, activated PECs are involved in inflammatory as well as degenerative glomerular diseases, which both can lead to irreversible loss of renal function.
    Seminars in Nephrology 07/2012; 32(4):357-67. DOI:10.1016/j.semnephrol.2012.06.007 · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. The reliability of current tests in predicting the onset, progression and response to various regimens for diabetic nephropathy is still under debate; and it has engendered a search for more sensitive and specific urinary biomarkers, especially those reflective of tubular dysfunctions. It is well-known that there is a good correlation between the degree of damage to the tubulo-interstitial compartment and the deterioration of renal functions. In view of this, the utility of urinary biomarkers, reflective of tubular injury, reported in the literature is discussed in this brief review.
    Endocrine 10/2012; 43(3). DOI:10.1007/s12020-012-9820-y · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AIMS: There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk. METHODS AND RESULTS: This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001). CONCLUSION: Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.
    European Journal of Heart Failure 12/2012; 15(4). DOI:10.1093/eurjhf/hfs187 · 6.58 Impact Factor
Show more