Kidney - Nephropathy, Chronic Progressive

Chronic progressive nephropathy, or CPN, is one of the most common spontaneous lesions and the single most important renal disease in rats and mice. The etiology of CPN is unknown, but factors such as strain, sex, age, diet, and hormones may modulate its occurrence and severity. The incidence and severity of CPN are generally greater in rats than in mice, and male rats are more severely affected than female rats. Nephropathy is both a degenerative and regenerative disease with characteristic morphology that is age dependent. It is a progressive disease and can lead to chronic renal failure and death. Early lesions can be seen in 2- to 3-month-old animals; by the end of 90-day studies, it is commonly observed in nearly all male rats.

Early lesions consist of focal to multifocal foci of tubule basophilia, nuclear crowding, peritubular basement membrane thickening, and variable infiltration by mononuclear inflammatory cells (Figure 1). As the disease progresses, the amount of affected renal parenchyma increases, individual components of CPN become more severe, and hyaline casts are prominent (Figure 2 and Figure 3). At the same time, glomerular changes, such as capillary tuft thickening, adhesions between the glomerular epithelium and Bowman’s capsule, and glomerulosclerosis, may be evident. CPN may progress to end-stage kidney disease, resulting in the death of the animal (Figure 4). CPN can often be exacerbated by chemical administration. The incidence and severity of CPN are generally less in the mouse than in the rat (Figure 5).

CPN is often accompanied by hyperplasia of the lining epithelium of the renal papilla. It is important to know that in advanced stages of CPN, there may be a small but significant increase in the incidence of proliferative lesions of the proximal tubule. Nephropathy is a bilateral lesion and differing severities of nephropathy between the two kidneys is rarely noted.