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Related Diagnoses

Chronic Progressive Nephropathy (CPN)
Progressive Glomerulonephrosis (PGN)
Chronic Glomerulonephropathy
Spontaneous degenerative nephropathy
Glomerulonephrosis
Chronic Progressive Nephrosis
Old Rat Nephropathy
Chronic renal disease
Chronic kidney disease
Renal insufficiency
Chronic uremia
Glomerulonephritis
Chronic interstitial nephritis

Definition

Progressive: to advance or move forward

Chronic: refers to a disease or condition of long duration, usually greater than six months, that progresses over time.

Nephropathy: any disease of the kidneys.

Clinical Signs

The disease due to its chronicity is often subclinical and is frequently only detected upon necropsy. Clinical signs often do not present until the rat has lost 75% of its kidney function.

For those clinical signs that do present, may see the following:

• Gradual weight loss (due to renal decompensation and uremia) even in the presence of an unchanged appetite.
• Lethargy (may be seen more in late to end stage)
• Increased drinking (polydipsia) and urination (polyuria)
• Changes in appetite
• Proteinuria (elevated protein in urine)
• Albuminuria (elevated albumin in urine)
• Palpably enlarged kidneys due to swelling initially. As condition progresses (becomes chronic) palpated kidneys will shrink, and become hard as they fibrose (become scarred).
• Hind limb weakness

Late to end-stage signs:

• Digestive disturbances (poor absorption of nutrients)
  • Loss of appetite
  • Intermittent loose stool/constipation

• Anemia (paleness may be observed in ears, around nose and mouth, toes, and teeth may appear whiter)
• Hypoproteinemia (low protein level in bloodstream)
• Azotemia (the accumulation of nitrogenous substances in the blood)
• Hypercholesterolemia (elevated level of cholesterol in bloodstream)
• Hydrothorax/Pleural effusion (serous fluid accumulating in one or both pleural cavities, the space between the ribs and the lungs)
• Ascites (accumulation of fluid in the abdominal cavity)
• Seizures (as kidneys fail)

*Note: for additional information on recognizing various signs of pain or discomfort refer to: Signs of Pain In Rats.

Etiology

The kidneys are paired organs lying one on each side of the spine and in back of the abdominal wall. Each kidney is composed of about million of tiny units called nephrons. Each one of these nephrons consists of a vascular component (the compact tuft of capillaries called the glomeruli) and a tubular component. The tubules are composed of epithelial cells that differ in how they function from one portion to another. It originates as a blind sac called Bowman's capsule that is closely associated on one side to the glomerulus. On the other side it opens into a coiled tubule called the proximal convoluted tubule, then into a hairpin-like loop known as Henle's loop, and then coils once again (called the distal convoluted tubule) before straightening as the collecting duct. Ultimately the collecting ducts of the tubules join to form larger ducts that empty into the renal pelvis (which is continuous with the ureter) and finally empties into the urinary bladder.

Chronic Progressive Nephropathy (CPN), as its name suggests, is a progressive disease of the renal tissue that results in degeneration and regeneration of the epithelium lining the tubules, a thickening of basement membranes in the capsule, interstitial inflammation and fibrosis, and lesions which may be found in the glomeruli that tend to be generalized with variability in the amount present.

Initially, the kidneys become enlarged (swell) and then as the condition advances begin to shrink and harden as they fibrose (scar) from the chronicity (long duration) of the disease.

Chronic Progressive Nephropathy is a commonly age-related disease in rats. Lesions may be present as early as 3 months of age (Harkness and Wagner, 1995), but become more severe in rats greater than 12 months of age. The incidence and increased severity of the disease occurs more frequently in the aging male rat than in female rats, and in certain lab species (namely F344 and Sprague-Dawley rats and to a much lesser degree in Wister and Long Evans hooded rats).

Some of the predisposing factors to this disease are: age, the male sex, strain/genotype, immunologic factors, endocrine involvement that increases prolactin levels, refined high protein diets, and feeding ad-libitum (which can also lead to obesity in rats), as well as the presence of certain chemicals and medications which may be toxic to the kidneys: all of these can affect the incidence and severity of the disease. In addition, diabetes (an example of endocrine involvement) can cause hyperglycemia which adds further insult to the kidneys.

Of those factors, the most important step in reducing the progression and severity of renal disease is controlling the amount of total dietary calories and protein. Dietary restrictions should not be implemented until the rat has reached 6 months of age. Rats fed high-protein diets are found to suffer greater nephron insult than those fed a reduced-protein diet. Such factors lead to the damage of the glomeruli (small capillary network in the kidney, a subunit of the nephron) within the kidney. This damage results in protein leaking from the kidneys into urine.

In addition, changes which occur in the tubular function of the kidneys and its urinary concentrating ability lead to large amounts of dilute urine being eliminated. As the kidneys become damaged they lose the ability to filter and remove waste products and extra fluids from the bloodstream.

CPN is a progressive, life-limiting disease ultimately resulting in disturbances in other systems of the body manifested as metabolic disturbances (e.g. acidosis), digestive disturbances (e.g. poor absorption of nutrients, changes in appetite, changes in the levels of normal flora of the gut), and anemia. Late stage disease has also been associated with extreme hypertension, polyarteritis nodosa, and secondary hyperparathyroidism resulting in generalized dystrophic mineralization. Death occurs due to renal (kidney) failure.

Moderate dietary reduction in the percentage of protein content and caloric intake may greatly reduce the incidence and severity of chronic glomerulonephropathy in rats as well as increase the survival in both sexes.

Care in the later stages is based on comfort measures until death ensues or until end of life decision must be made.

Figures

Case History and Photos

• Fig. 1: Glomerulonephritis in 20-month-old male rat- Martin

Diagnostics

Lab:

• BUN (normal range: 12-20mg/decileter, CREATININE (normal range: 0.3-0.4mg/decileter).
• Specific gravity (normal range: 1.04 -1.07) Please note however, that BUN and SG may not be useful markers as results may be unchanged until disease near end stage at which time these results may increase. *Note: that SG may remain at a constant reading when renal disease is presence.
  Urine dipstick for pH 8-8.5 and proteinuria (greater than 300mg/dl of urine) are the best indicators of renal disease in the rat.

• Metabolic acidosis, increased potassium and phosphorus levels, and decreased calcium levels in advanced disease.
• Histology reports may show white or pale tan kidneys with thick glomerular capillaries, dilated tubules, interstitial fibrosis, albuminous or proteinaceous casts, and pitted surface. Urine will reflect elevated amounts of protein.

Treatment

Treatment is primarily palliative. There is no cure for the disease; however, treatment should be supportive to help reduce the development of complications caused from hypertension, elevated potassium levels, metabolic acidosis, and urinary tract infections due to bacteria.

A 10-14% low protein, low phosphorus diet, supplemented with omega-6 and omega-3 polyunsaturated fatty acids and conjugated linoleic acid (found in flax seed) have been found to be beneficial in the management of rats with kidney disease.

Promote acidifying urine with healthy diet.

Avoid over-feeding. Reduce obesity gradually if the rat is over weight.

Encourage hydration by providing easy access to source of water, and adding additional juicy type fruits in the diet.

Consideration may be given to the use of anabolic steroid medications (although rarely used), and vitamin B-complex, both of which may help to improve the production of red blood cells and to improve appetite.

Warmed subcutaneous fluids may be given if additional fluids are required to aid in flushing waste products from the blood. In addition, a diuretic such as Lasix (furosamide) may be given to promote the elimination of waste products in urine.

Aluminum hydroxide antacid, when deemed appropriate, may help to improve digestion and remove excess amount of phosphorus from the body.

In the event there is a co-existing infection, treatment should include antibiotics.

Consideration may be given to the use of antihypertensive medication such as ACE inhibitors (e.g., enalapril), or a calcium-channel blocker.

For information pertaining to medications refer to the Rat Medication Guide.

Nursing Care

• Maintain adequate hydration.
• Monitor skin turgor daily. Gently pinch up skin behind neck and release. A well-hydrated rat's skin will return to place quickly, but if the rat is dehydrated the return will be much slower.
• Provide a low protein, low phosphorus diet, designed specifically for rats. Avoid ad libitum feeding. Reduce obesity gradually.
• Include daily probiotic (may use probiotics for human use, e.g. lactobacillus, bifidobacter). Rats maintaining adequate normal gut flora tend not to develop renal failure. It has been recommended to use probiotics early in life.

Outcome

• Dehydration prevented.
• Protein decreased in diet.
• Obesity in rat reduced gradually.
• Rat's comfort maintained.

Prevention

• Regular health checks, maintaining a healthy weight, reducing obesity, and treating illnesses as they arise can go a long way to reducing the tendency toward development, or severity of the disease.

Consultation

• Gregory W. Lawson DVM, PhD, DACLAM; Division of Laboratory Animal Medicine; Director/Pathology and Laboratory Medicine; David Geffen School of Medicine at UCLA

References

1. Hines, R. “Treatment of Rat Kidney Disease.” 2ndchance.info. http://www.2ndchance.info/ratkidney.htm (accessed November 6, 2009).
2. Additional resources used for this article listed in References of the Health section of the Rat Guide, http://ratguide.com/health/reference/references.php

   Posted on October 29, 2009, 12:22, Last updated on June 2, 2010, 19:14 | Urinary / Renal