Quantitative and Qualitative Urinary Cellular Patterns Correlate with Progression of Murine Glomerulonephritis

Justin Brown,Junpei Kimura,Saori Otsuka,Tomonori Kanazawa,Osamu Ichii,Yasuhiro Kon,Yuka Namiki,Yoshiharu Hashimoto

doi:10.1371/journal.pone.0016472

Abstract

The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.

Highlights

Lack of renal disease control is an inevitable problem in clinical medicine because the kidney is a nonregenerative organ
Chronic glomerulonephritis (CGN), which begins with glomerular lesions (GLs), is one of the major chronic kidney disease (CKD) that is primarily caused by certain infections, drugs, and systemic disorders [2,5]
Glomerular damage score was used as an index of GLs and was comparable to urinary cell number, suggesting that the number of urinary cells significantly increased with glomerular damage score (Fig. 2c)

Summary

Introduction

Lack of renal disease control is an inevitable problem in clinical medicine because the kidney is a nonregenerative organ. The global population of patients with end-stage renal disease (ESRD) has recently been increasing [1]. Several studies have indicated that chronic kidney disease (CKD) is strongly associated with ESRD progression [2,3,4], and the rapid increase in the number of patients with CKD has become a worldwide public health problem. Chronic glomerulonephritis (CGN), which begins with glomerular lesions (GLs), is one of the major CKDs that is primarily caused by certain infections, drugs, and systemic disorders [2,5]. In the early stages of CGN, glomerular immune-complex depositions cause GLs, such as capillary barrier disruption, which lead to ultrafiltration of plasma proteins or protein-associated factors [5]. CGN progresses to ESRD through a final common pathway in which progressive interstitial fibrosis is associated with tubular atrophy and peritubular capillary loss [5]

Methods

Results

Conclusion