Proteinuria in chronic kidney disease in the cat: any hope for effective management?
This paper is about proteinuria in the cat. The cause of proteinuria is most likely chronic kidney disease (CKD). Nowadays there are more cats with this complication. Therefore it is necessary to do more research; it is a very common disease. For the practice it is significant how to treat and managing this disease. There is a staging system for this disease, divided in four stages. It is important to know as a vet in which stage the cat is, because then they know which treatment the cat needs. When there are signs for kidney failure, it means that a lot of kidney tissue is damaged. One kidney can compensate for the other kidney when this one is damaged.
The normal function of the kidneys is to keep the extracellular fluid stable, for the homeostasis. Glomerular filtration, followed by tubular reabsorption and secretion take care of maintaining the homeostasis. Also have the kidneys a role for hormones, the kidney is an endocrine organ. If there is renal failure, it can cause a dysfunction of the role of the kidney.
Proteinuria is an abnormal amount of protein in the urine. The cause can be pre-renal, renal or post-renal. This will be discussed later.
In this paper it is discussed how this disease arises and what the symptoms are. How renal failure should be treated. And in which stage renal failure found oneself. There are tests that can be done, for example urine test or blood test, to found out in which stage the disease is. Also there will be described how to treat a cat with renal disease. How proteinuria does arises, caused by renal disease. And how renal failure begins, what the causes are.
Renal disease is most of the time progressive. So an early diagnosis of this disease and kidney failure and with the right treatment can slow down of the sickness process. Treatment of patients with end-stage renal disease is difficult. Patients with end-stage renal disease (ESRD) therefore are the only effective treatment a renal replacement, like renal transplantation or dialysis.
Veterinarians must be able to rapidly diagnose the early stage of renal failure, and then the patients can have the most optimal treatment. There are two large advantages to an efficient treatment. First, there is less damaged kidney tissue in an early stages and more function left. An early start of the treatment will give a greater impact on survival time; the survival time will most likely be longer. (2)
The localization of the causes of proteinuria can be pre-renal, renal or post-renal.
Pre-renal proteinuria: the glomerular barrier is facing an increased concentration of protein of low molecular weight. These proteins can easily get through the glomerular barrier into the primary filtrate. In healthy animals, some of the small proteins will filtered because of the glomerular barrier. The proximal tubular epithelium provides reabsorption of proteins from the primary glomerular filtrate. This result in that there are almost no proteins is present in the urine. When there is an increased concentration of proteins, the reabsorption fails and can result in proteinuria. (3)
Renal proteinuria: severe proteins in urine can be caused by glomerular dysfunction. Glomerulonephritis, amyloidosis and inherited glomerulopathies are different kinds of glomerular diseases. Glomerulonephritis in cats can cause severe proteinuria. Amyloidosis is most seen in Abyssinians, and inherited glomerulopathies are not documented in the cats. Not only has the function of the barrier, but also the hydrostatic pressure has an effect on the amount of protein that passes the glomerular barrier. When this pressure is increased, so there is glomerular hypertension, more proteins can pass the glomerular barrier into the urine. The most likely cause of glomerular hypertension is systemic hypertension. Ultimately results in glomerular hyperfiltration, because the number of functioning nephrons decreases and the remaining nephrons take over the function. The remaining nephrons must filter a greater volume of plasma with an increased pressure. Short term, this leads to preservation of glomerular filtrate, but longer term, it results in loss of nephrons. This process can lead to progression of renal disease. (3)
Post-renal proteinuria: the proteins in the urine coming from the track after the kidney. The most common cause is an inflammation of the bladder. Other causes can be urolithiasis, tumors or contamination by urine collection. The cause of post-renal proteinuria is usually haematuria. Proteins are present in blood, which leads to proteinuria. (3)
There are four stages of feline chronic kidney disease.
In stage 1:
non-azotemia. The cat has markers of kidney damage. Plasma creatinine is less than 140µmol/l.
In stage 2:
Mild renal azotemia. The cat has markers of kidney damage. Plasma creatinine is between 140 and 249µmol/l.
In stage 3:
Moderate renal azotemia. Plasma creatinine is between 250 and 439µmol/l.
And in stage 4:
severe renal azotemia. Plasma creatinine is equal or more than 440µmol/l. (1)
Staging of chronic kidney disease of the International Renal Interest Society's (IRIS):
Stage I is not included in this study. Stage II: cats with creatinine concentration between 1.6 and 2.8mg/dL. Only cats with creatinine concentration above 2.3 were aloud in this study. So therefore stage II is divided in two groups. Stage IIa: with creatinine concentration between 1.6 and 2.2mg/dL, and stage IIb: with creatinine concentration between 2.3 and 2.8mg/dL. Stage III: cats with creatinine concentration between 2.9 and 5.0mg/dL. And stage IV: creatinine concentration more than 5.0mg/dL. In this study there are 211 cats. Regardless at what stage, the mean age for all cats is 12.8 years. Table 1 shows in which stage a cat is present.
Table 1. Survival (in days) of cats based on stage of CKD at the time of diagnosis.
Stage of diagnosis number of cat's percentage of cat's survival median(95%CI)
IIb 78 37 1151
III 69 33 778
IV 64 30 103
Table 2 shows that after fluid therapy cats where placed in other stage, because the prerenal component of azotemia can be corrected with fluid therapy. Because of the fluid treatment, tree of the 211 cats are no longer present in stage IIb, but probable in stage IIa or stage I. These stages are not included in this study.
Table 2. Survival (in days) of cats based on stage of CKD determined after correction of prerenal azotemia.
Stage at baseline number of cat's percentage of cat's survival median(95%CI)
IIb 82 39.4 1151
III 84 40.3 679
IV 42 20.2 35
Of the 211 cats, 158 were euthanized and 53 cats died of natural causes. Of the 211 cats, 121 cats developed anemia before death. In 142 cats have lost weight before death, from the point weight loss began; the survival time was 401 days. There were 22 cats that did not lose weight, and in 47 cats it is unknown whether they lost weight.
Of the 211 cats, 135 cats have reached the point of clinical decompensation. The survival time from decompensation to death is 40 days. Or the 54 cats have reached decompensation is unknown. The other 22 cats did not reach decompensation. When the cat was diagnosed for CKD, other variables were measured, like age, albumin, BUN, creatinine, calcium, bicarbonate, potassium, and hematocrit. These variables were not found predictive of survival. Only was serum phosphorus was predictive of survival. If level phosphorus in blood increases 1U, increases the risk of dead by 11.8 percent. This study shows that IRIS stage of renal disease, based on serum creatinine, gives a strong indication of survival time in cats.
After fluid therapy cats are placed in other stage, because the prerenal component of azotemia can be corrected with fluid therapy. This is staging at baseline, rather than at diagnosis. But staging at baseline probably gives a more represent the correct stage of renal disease and prognosis for survival. (4)
One of the very common cause of illness and death is cats, is chronic renal failure. The prevalence of kidney failure increase with at least 15 percent of cats over the age of 15 with azotemia. There are different kinds of causes for renal failure, including polycystic kidney disease, obstructive ureterolithiasis, renal lymphoma, pyelonephritis, and amyloidosis. But at postmortem examination is diffuse tubulointerstitial nephritis the most frequent histopathologic description of kidney tissue. If cats have strongly increased plasma creatinine concentration at diagnosis, the survival time is most likely shorter. The survival time increases when the cat with chronic kidney failure is fed with a diet restricted in protein and phosphate. (5)
In this study was examined what factors affect proteinuria in cats with variable renal function and to see whether these factors impair the survival time. Also because in humans and dogs with hypertension and renal disease, have more proteins in the urine, and proteinuria is an important predictor of progression. The influence of hypertension was therefore specifically examined in the cat. Therefore, the urine protein-to-creatinine ratio (UPC) and the urine albumin-to-creatinine ratio (UAC) were measured. This study included 28 normal cats, 14 with hypertension but plasma creatinine concentration within the range of IRIS staging, and 94 cats with azotemia, 28 of whom were also hypertensive, so in total data of 136 cats was used. But of 10 cats the ages was unknown, so they were excluded from this study. Of the 126 cats, 55 cats died, of which 50 were euthanized. This study suggests a relation between plasma creatinine concentration and systolic blood pressure and magnitude of proteinuria in cats. In human patients was found an independent association of plasma creatinine concentration with the magnitude of proteinuria in an early study, which is comparable with this study of proteinuria in the cats. In another study there was found, if the renal mass is reduced, UPC increases. This can be explained by the consequences of declining renal function, with afferent arteriolar vasodilatation, resulting in increased glomerular capillary pressure. (5)
More intact proteins in the urine are the result of less number of functioning tubules, because of decreasing of renal function. If there are fewer functioning tubules, less reabsorption takes places and reduces the filtered proteins. But also because of the fewer functioning tubules, there is less surface area over which proteins may lose, thus limiting the rise in protein excretion. A cat with kidney failure also suffer from loss of muscle mass, when this happens the creatinine concentration is higher. So creatinine concentration is a poor indicator of glomurular filtration ratio (GFR). By treatment of hypertension, glomerular hypertension may be induced. In this study there is no indication of age as a risk factor for increasing proteinuria. This is because when a cat gets older, the muscle mass declines, and therefore creatinine excretion tends to decrease. But there could be an increasing in UPC and UAC because of a reduction in urinary creatinine excretion. The sex of the cats does not affect the amount of proteins in the urine. Creatinine concentration, age and protein excretion were all independently associated with shorter survival times in this study. (5)
1) Roudebush, ,P., Polzin, D.,J., Ross, S.,J., Towell, T.,L., Adams, L.,G. & Forrester, S.,D. "Therapies for feline chronic kidney disease. What is the evidence?"
2) Lees, G.E. 2004, "Early diagnosis of renal disease and renal failure", The Veterinary clinics of North America.Small animal practice, vol. 34, no. 4, pp. 867-85, v.
3) Syme, H.M. 2009, "Proteinuria in cats. Prognostic marker or mediator?", Journal of feline medicine and surgery, vol. 11, no. 3, pp. 211-218.
4) Boyd, L.M., Langston, C., Thompson, K., Zivin, K. & Imanishi, M. 2008, "Survival in cats with naturally occurring chronic kidney disease (2000-2002)", Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, vol. 22, no. 5, pp. 1111-1117.
5) Syme, H.M., Markwell, P.J., Pfeiffer, D. & Elliott, J. 2006, "Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria", Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, vol. 20, no. 3, pp. 528-535.