
Get access to all handy features included in the IVIS website
- Get unlimited access to books, proceedings and journals.
- Get access to a global catalogue of meetings, on-site and online courses, webinars and educational videos.
- Bookmark your favorite articles in My Library for future reading.
- Save future meetings and courses in My Calendar and My e-Learning.
- Ask authors questions and read what others have to say.
Pathophysiology
Get access to all handy features included in the IVIS website
- Get unlimited access to books, proceedings and journals.
- Get access to a global catalogue of meetings, on-site and online courses, webinars and educational videos.
- Bookmark your favorite articles in My Library for future reading.
- Save future meetings and courses in My Calendar and My e-Learning.
- Ask authors questions and read what others have to say.
Read
2. Pathophysiology
Most of the nephrons of the diseased kidney fall into one of two categories. They are either non-functioning nephrons, as a result of destruction of any portion of their structures, or they are intact nephrons that function normally. Changes in renal function occur as a result of a reduction in the number of functioning nephrons. As the number of functioning nephrons diminishes, there are adaptations that occur in a regular sequence. When nephrons are damaged and essentially rendered non functional, the remaining "healthy" nephrons increase their size and their work load to compensate for nephron loss. This is referred to as the hyperfiltration theory (Figure 3). Nephron hypertrophy and hyperfiltration is an adaptative mechanism to compensate for reduced nephron number.
Figure 3. Central role of glomerular hypertension in the initiation and progression of nephron injury.
Nevertheless the chronic increase in glomerular capillary pressure and/or glomerular plasma flow rate damages the endothelium, mesangium and epithelium. Mesangial matrix production, glomerular deposition of circulating lipid, and capillary thrombosis promote structural injury to the glomerulus. Tubulointerstitial damage, increased tubular ammoniagenesis, and soft tissue mineralization contribute to nephron injury and ultimately lead to nephron sclerosis. Continued nephron destruction initiates further compensation, promoting a self-perpetuating cycle of adaptation and injuries (Figure 4).
Figure 4. Illustration of the relationship between renal injury, loss of nephrons, renal compensatory adaptations, and the ultimate progression.
The progression of CRF has been described as occurring in four stages that are not sharply demarcated but rather, are phases in a continuing degenerative process with loss of more and more functioning nephrons (Table 2).
Table 2. International Renal Interest Society (IRIS) Classification of Stages of Renal Disease and Chronic Renal Failure in Dogs. | ||||
Stages | I | II | III | IV |
Plasma Creatinine μmol/L mg/dL | > 440 > 5.0 | < 125 < 1.4 | 125 to 180 1.4 to 2.0 | 181 to 440 2.1 to 5.0 |
The four phases are: (1) decreased renal reserve, (2) renal insufficiency (3) renal failure (4) uremic syndrome. |
Given the large reserve capacity of the kidney at least 60 - 70% of normal renal function must be lost before azotemia increases, although there may be some nephron hypertrophy during the first phase of decreased renal reserve. At this stage, the patient does not have any clinical symptoms although decreased urine concentrating ability may be noted. In renal insufficiency, up to 75% of the nephrons may be lost. There is mild azotemia, loss of urine concentrating ability and the patient becomes more susceptible to the effects of stresses such as large changes in fluid intake, protein and electrolytes. The patient may remain symptom-free if no overwhelming metabolic stress occurs.
In renal failure nephron loss may reach 90%. There is moderate to severe azotemia, anemia, decreased urine concentration ability and impaired ability to maintain electrolyte and acid base balance.
The pathogenesis of the uremic syndrome is complex and not fully understood. Many toxins are involved and no single compound is likely to explain the diversity of the uremic symptoms. Nitrogenous waste products of protein digestion and catabolism (e.g. urea, creatinine, ammonia, middle molecules, guanidine and its derivatives) accumulate when renal function is reduced and some of them contribute to many of the clinical consequences of uremic intoxication associate with chronic renal failure (Table 3).
Table 3. Examples of Toxins Implicated in the Uremic Syndrome | |
Oxalic acid Parathyroid hormone β-2 microglobulin Methylguanidine Guanidinosuccinic acid | Dimethyl arginine Amines Phenols Indoles Pseudouridine |
Get access to all handy features included in the IVIS website
- Get unlimited access to books, proceedings and journals.
- Get access to a global catalogue of meetings, on-site and online courses, webinars and educational videos.
- Bookmark your favorite articles in My Library for future reading.
- Save future meetings and courses in My Calendar and My e-Learning.
- Ask authors questions and read what others have to say.
1. Adams LG. Phosphorus, protein and kidney disease. Proceeding of the Petfood Forum 1995 (13-26).
2. Bauer JE, Markwell PJ, Rawlings JM et al. Effects of dietary fat and polyunsaturated fatty acids in dogs with naturally developing chronic renal failure. J Am Vet Med Assoc 1999; 215: 1588-1591.
About
How to reference this publication (Harvard system)?
Affiliation of the authors at the time of publication
1Royal Canin USA, MO, USA. 2Experimental Physiopathology and Toxicology, National Veterinary School of Toulouse, Toulouse, France.
Comments (0)
Ask the author
0 comments