Nephritic disease and nephritic failure are among the most common conditions impacting cats, peculiarly during the ulterior old ages of life. In fact, kidney disease is normally listed among the major concerns of proprietors of geriatric pets as nephritic disease can be associated with important morbidity and mortality. Over the past 20 old ages, considerable advancement has been made in the diagnosing and intervention of many nephritic conditions and the apprehension of nephritic disease and how to name and pull off patients continues to germinate. Notably, the accent on clinical research to work out clinical jobs, has doubtless lead to improved patient attention and quality of life.
Nephritic disease may be defined as any harm, microscopic or macroscopic, that reduces the operation of one or both kidneys ; of which the badness of disease depends greatly on the extent of nephritic involvement1. Chronic nephritic disease is a progressive irreversible status in worlds and comrade animate beings that leads to uremia and finally decease within months to old ages after the initial diagnosing. In the felid patient, the rate of patterned advance is extremely variable with long periods of clinically stable nephritic map being possible with proper medical and nutritionary direction. It is of import to observe, nevertheless, that therapy should be individualized based on rating of the patient ‘s historical, physical, and diagnostic findings. Additionally, responses to therapy and proprietor conformity are of great consideration and importance in decelerating the patterned advance and bettering the quality of life of cats with chronic nephritic disease.
Physiology – Overview
Two major maps of the kidneys are to egest metabolic waste merchandises and to modulate the volume and composing of the organic structure ‘s extracellular fluid. Additionally, the kidneys are responsible for the secernment of endocrines and hydrolysis of little peptides. These endocrines and peptides participate in the ordinance of systemic and nephritic kineticss, ruddy blood cell production, and Ca, P and bone metabolism2,3. In order for the kidneys to adequately execute these maps, fluid must be filtered from the glomerular capillaries into the nephritic tubules in a procedure called glomerular filtration. As the glomerular filtrate flows through the tubules, the volume of the filtrate is reduced and its composing is altered by cannular resorption and by cannular secernment, each of which is extremely variable depending on the organic structure ‘s demands. Thus elimination of each substance in the urine involves a specific combination of filtration, resorption, and secernment. Each of these procedures is physiologically controlled and alterations in the elimination rate occur via alterations in glomerular filtration, cannular resorption and cannular secretion2.
Nephritic blood flow constitutes about 22 % of the cardiac end product. Two alone characteristics of nephritic circulation are the high rate of blood flow relation to weave mass and the presence of two capillary beds: the glomerular and peritubular capillaries. The peritubular capillaries are arranged in series and are separated by motorial arteriolas. The glomerular capillaries filter big sums of fluid and solutes, most of which are reabsorbed from the nephritic tubules into the peritubular capillaries. Both glomerular filtration rate and nephritic blood flow are autoregulated during alterations in arterial force per unit area. A cardinal constituent to the autoregulation is tubuloglomerular feedback, which depends on the juxtaglomerular composite, a particular anatomic agreement of sunspot densa cells in the distal tubule and juxtaglomerular cells in the walls of the sensory nerve and motorial arteriolas. When blood force per unit area is decreased, bringing of Na chloride is decreased to the sunspot densa cells which, in bend, do a lessening in opposition of the sensory nerve arteriolas and activation of the renin-angiotensin-system2. When the blood supply to the kidney is compromised, important nephritic harm can ensue.
The functional unit of the kidney is the uriniferous tubule which is comprised of the glomerulus, where big sums of fluid are filtered from the blood, Bowman ‘s capsule, and the nephritic tubule where filtered fluid is converted to urine on its manner to the nephritic pelvic girdle, which receives piss from all the uriniferous tubules. The nephritic tubule is subdivided into five major subdivisions: the proximal tubule, the cringle of Henle, the distal tubule, the connecting tubule, and the medullary collection duct2.
Pathophysiology- Damage to the Nephron & A ; Renal Disease
Severe kidney disease can be divided into two chief classs: acute nephritic failure, in which the kidneys suddenly stop working wholly, or about wholly, but may finally retrieve about normal map ; and chronic nephritic failure, in which there is progressive loss of map of uriniferous tubules that bit by bit decreases overall kidney map. There is another class, which falls under chronic nephritic failure, termed “ acute upon chronic nephritic failure ” 4 where there is acute decompensation of the inveterate morbid kidneys. Within the two aforementioned major classs, there are many specific kidney diseases that can impact the blood vass, glomeruli, tubules, nephritic interstitium, and parts of the urinary piece of land outside the kidney2.
Acute nephritic failure may be divided into specific classs: prerenal ague failure, intrarenal ague nephritic failure and postrenal ague nephritic failure. Prerenal acute failure can be a effect of any status that causes the blood flow to the kidney to fall to less than 20 % of normal, at which point the nephritic cells become hypoxic. Further lessenings in blood flow, if prolonged, do harm or decease to the nephritic cells. If the acute nephritic failure is non corrected, this type of failure can germinate into intrarenal acute nephritic failure. Intrarenal acute nephritic failure can be the consequence of any abuse to the kidney, including the blood vass, glomeruli, or tubules. Examples of such abuses include acute glomerulonephritis ; acute cannular mortification caused by terrible nephritic ischaemia and toxins or medicines that damage the cannular epithelial cells. If the harm is non excessively terrible, some regeneration of the cannular epithelial cells can happen, and nephritic map may be restored. If the acute redness does non lessen in a timely mode, the glomeruli or tubules become destroyed beyond fix which leads to a progressive chronic nephritic failure province. Postrenal acute nephritic failure occurs when there is some kind of obstructor of the urinary collection system. Important causes of obstructor in the feline patient include: urethral rocks, vesica rocks, or idiopathic felid lower urinary piece of land disease2,4,5.
Chronic nephritic failure occurs when there is irreversible harm to the kidney that causes a lessening in the figure of functional uriniferous tubules. Serious clinical marks of chronic nephritic failure do non happen until the figure of functional uriniferous tubules falls to at least 75 % below normal4,5. The care of normal plasma concentrations of electrolytes and normal organic structure fluid volumes occurs at the disbursal of systemic compensations, such as high blood pressure. In general, chronic nephritic failure, like acute nephritic failure, can happen because of upsets of the blood vass, glomeruli, tubules, nephritic interstitium, and lower urinary piece of land. Despite the broad assortment of diseases that can do chronic nephritic failure, the terminal consequence is the same- a lessening in the figure of functional nephrons4.
The loss of functional uriniferous tubules requires the lasting uriniferous tubules to egest more H2O and solutes. The kidneys usually filter a big volume of unstable each twenty-four hours at the glomerular capillaries and so transform this filtrate to urine as the fluid flows along consecutive uriniferous tubule sections. Regardless of figure of functional uriniferous tubules, the kidneys must egest the same volume of urine to keep unstable balance. The loss of functional uriniferous tubules hence requires the lasting uriniferous tubules to egest excess sums of H2O and solutes to forestall accretion of these substances in the organic structure fluids. This is achieved by increasing the GFR ( glomerular filtration rate ) or diminishing the cannular resorption rate in the surviving uriniferous tubules. These versions allow H2O and electrolyte balances to be maintained with small alteration in extracellular volume or electrolyte composing. In contrast to the electrolytes, many of the waste merchandises of metamorphosis such as urea and creatinine accumulate about in proportion to the figure of uriniferous tubules that have been destroyed. These substances are non thirstily reabsorbed by the nephritic tubules, and their elimination rate depends mostly on the glomerular filtration rate. If the GFR lessenings, these substances accumulate in the organic structure, increasing the plasma concentration. Other substances such as phosphate and H ions are maintained near normal until the GFR falls below 20-30 % of normal2,5.
The consequence of nephritic failure on the organic structure can be lay waste toing. Common sequelae include: H2O keeping and development of hydrops ( nephroitic syndrome ) and azotemic syndrome. These pathophysiological alterations that occur in chronic nephritic disease can be attributed to the compensatory mechanisms of the staying uriniferous tubules. Uremic syndrome comprises a multitude clinical marks that include Na and H2O instability, anaemia, saccharide intolerance, neurological perturbations, GI piece of land perturbations, osteodystrophy, immunological incompetency, and metabolic acidosis5.
Anemia consequences from an unequal sum of erythropoietin being produced by the kidneys and decreased ruddy blood cell life span. Erythropoietin is an of import endocrine responsible for exciting the bone marrow to bring forth ruddy blood cells. The anaemia that consequences is typically a normochromic, normocytic non-regenerative anemia2,4,5,6.
Gastrointestinal piece of land perturbations include irregularity ensuing from desiccation because of unequal H2O consumption to equilibrate the inordinate fluid loss in urine5 and nonspecific marks such as gastritis, sickness, anorexia and purging attributable to inadequate clearance of gastrin from the kidneys7.
Osteomalacia is the consequence of unequal sums of the active signifier of vitamin D ( calcitriol ) being produced which finally leads to reduced enteric soaking up of Ca and reduced handiness of Ca to cram. Finally, bone is partly absorbed and becomes greatly weakened. Another of import cause of demineralisation of bone in chronic nephritic failure is the rise in serum P concentration because of reduced GFR. Elevations in serum P additions binding of P with Ca in the plasma and decreases serum ionised Ca. The terminal consequence is extra parathyroid endocrine secernment, increased release of Ca from bone and farther demineralization2,5,6,8,9.
The pathophysiology of metabolic acidosis is complex and is related to protein consumption from the diet, but can be summarized to be the consequence of reduced nephritic sulphate and phosphate elimination secondary to reduced GFR, decreased H ion secernment and nephritic ammoniagenesis, and increased urinary hydrogen carbonate loss5.
Clinical Signs, Physical Examination, Nosologies
Nephritic inadequacy is merely evident clinically when overall nephritic map is impaired to a point where the kidneys fail to forestall the buildup of metabolites ; this normally follows the loss of 75 % of nephritic functional mass. Clinically, because of this, in the early phases of nephritic disease, many patients are symptomless or exhibit merely elusive clinical marks. Some of the most common clinical marks and historical findings observed in cats with chronic nephritic disease include: weight loss, anorexia, desiccation, polydipsia, polyuria, periodontic disease, halitosis with unwritten ulceration, purging, palpably little kidney ( s ) , depression, pale mucose membranes, musculus failing and pace abnormalcies, cervical ventroflexion, and optic marks related to systemic hypertension4,5,8,9. Once grounds of nephritic disease has been identified, it is frequently desirous to desire to find whether the evident nephritic disfunction is acute or chronic. However, in the absence of historical research lab informations, the physical scrutiny, current research lab informations, and imaging surveies to measure nephritic size, form and architecture must be used to find the chronicity and phase of the dysfunction5.
In cats adequate urine-concentrating ability is defined as a urine specific gravitation of 1.035 or greater. Detection of urine specific gravitation greater than 1.035 in absence of important albuminurias is normally a dependable index that chronic nephritic disease is non present. If urine specific gravitation is less than 1.035 or if albuminurias is present, chronic nephritic disease can non be ruled out and extra rating is indicated. Increased blood urea N ( BUN ) and creatinine ( uremia ) concentrations together with a urine specific gravitation of 1.007 -1.030 ( normally 1.007-1.015 ) is considered presumptive grounds of nephritic disease. Other clinical pathological findings that may be present include, but are non limited to: hyperphosphatemia, hypokalemia, hyper- or hypocalcaemia, metabolic acidosis, normochromic, normocytic nonregenerative anaemia, albuminuria as evidenced via a urine protein: creatinine ratio, and systemic hypertension4,5,6,9.
Staging the Disease- IRIS
The International Renal Interest Society was created in 1998, by a group of veterinary nephrologists and funded by NovartisA® Animal Health, with the mission to help veterinary practicians in the apprehension, diagnosing and intervention of nephritic disease in the comrade animate being. Out of this enterprise, IRIS has established an internationally recognized set of presenting guidelines has outlined the diagnosing, appraisal and intervention of nephritic disease based on at least two consecutive blood plasma creatinine concentrations. Sub-stages utilizing this system are based on the grade of albuminuria and systemic blood pressure10. Prior to the constitution of the IRIS theatrical production system, veterinary practicians had subjectively classified chronic nephritic disease as mild, moderate, or severe based on laboratory findings and clinical marks. While the IRIS theatrical production system is besides slightly arbitrary, it does look to turn out utile for set uping forecast and managing patients with chronic nephritic disease.
Treatment- Medical Management
Medical direction of chronic nephritic disease should be focused on supportive and diagnostic therapy that non merely addresses abnormalcies in fluid, electrolyte, acid-base, hormone and nutritionary balance but besides aims to decrease the clinical and pathophysiological effects of reduced nephritic map. Clinical marks or uraemia should be addressed and attempted to be corrected before originating long term medical management1,11,12,13,14,15. Treatment of nephritic failure may include a figure of curative manoeuvres that can be effectual in decelerating the intrinsic patterned advance of the disease. These include dietetic protein limitation, angiotonin change overing enzyme ( ACE ) inhibitors, alteration of dietetic lipid consumption and phosphate limitation, Ca channel blockers, hypodermic fluid disposal, vitamin and electrolyte addendums, and recombinant human erythropoietin ( rHuEPO ) 1. Evidence for a good consequence on endurance for each of these interventions is limited and hence presently each instance should be assessed on an single basis16, 17,18.
Care of hydration should be a top precedence in those patients with nephritic disease. Unrestricted entree to H2O is indispensable to let thirst to counterbalance for obligatory polyuria. Extra fluids ( unwritten, hypodermic, or endovenous ) may be required when intake fails to maintain gait with diuresis. Home disposal of hypodermic fluids are indicated when the cat is unable to keep hydration. Education of the proprietor on proper disposal and unfertile technique is vital15.
Treatment of cats with chronic nephritic disease by dietetic alteration has been proven to significantly increase survival17,19,20. By and large, commercially available nephritic diets are recommended. These diets have restricted protein, Ca, Na, P, and acid-base burden, and added K. There are many commercially available diets that meet the nutritionary demands of the nephritic patient: Hill’sA® k/d, Royal CaninA® LP, and PurinaA® n/f. Dietary protein limitation in moderate to severe chronic nephritic failure is often advocated to help in cut downing the accretion of nitrogen-bearing waste merchandises that are believed to lend to azotemic syndrome19,20. Poor appetency and the reduced palatableness of restricted protein diets make malnutrition a serious job in nephritic failure patients15. Weight loss and diminishing musculus mass should be carefully monitored.
Angiotensin-converting enzyme ( ACE ) inhibitors may hold a renoprotective consequence, which is independent of any consequence on systemic blood pressure21. ACE inhibitor therapy with benazapril 0.25-0.5 mg/kg PO q24h may besides be utile in cut downing the grade of albuminuria in cats with chronic nephritic failure22, The mechanism of these effects are ill-defined, but may be hemodynamically mediated by doing nephritic vasodilation particularly of the motorial arteriola, and cut downing glomerular capillary pressure21,23. Preliminary surveies of ACE inhibitor usage in of course happening chronic nephritic failure in cats have shown important increased survival times for the subgroup of nephritic failure cats with urine protein: creatinine ratios & gt ; 116, 22,23. By cut downing glomerular force per unit area, ACE suppression would be expected to do a lessening in glomerular filtration rate and so may increase uremia, therefore it is recommended that an addition in creatinine & gt ; 50 % warrants backdown of the drug23.
Treatment of nephritic secondary hyperparathyroidism should be instituted in a staged mode. The basis of therapy is dietetic phosphate limitation. The purpose of dietetic limitation of phosphate is to cut down plasma P to the lower terminal of the mention scope, the point at which the most effectual control of PTH secernment is normally attained. If after some clip dietetic direction entirely is non take downing the serum P or the PTH degree is non diminishing, so enteric phosphate-binding agents should be introduced to further curtail phosphate consumption. Intestinal phosphate binding agents organize non-absorbable salts of phosphate, adhering phosphate in both the diet and enteric secernments. To accomplish efficient phosphate binding, the medicine should be given, ideally assorted with or given instantly anterior to feeding. The usual drug of pick is aluminum hydrated oxide ( 30-100 mg/kg/day PO ) and can be compounded if necessary to better patient compliance13,14. High dietetic phosphate limits the effectivity of phosphate-binding agents, so sooner these should be used in combination with a commercially available nephritic diet5,8.
Additionally, secondary nephritic hyperparathyroidism can be treated with an active signifier of vitamin D, which will straight suppress PTH secernment. Calcitriol ( 1.5-3.5 ng/kg/day PO ; max 10 ng/kg/day ) acts to heighten enteric soaking up of Ca and P, and so are contraindicated unless plasma concentrations of Ca and P are normal. It is of import to observe that calcitriol therapy will be uneffective in diminishing PTH concentration if P is elevated. Phosphorus concentration must be below 6 mg/dl before calcitriol usage is optimum. At serum P degrees of 6-7 mg/dl, the effectivity of calcitriol is decreased, and at a P greater than 8 mg/dl it is uneffective in cut downing PTH concentration. Plasma ionised Ca must be closely monitored and the dose of calcitriol should be titrated to keep normocalcemia and should be discontinued if hypercalcemia occurs5,9,11. PTH concentrations should be measured to document successful control of nephritic secondary hyperparathyroidism. The long term advantages of this therapy are unproved as of yet, but the purpose is to diminish patterned advance of nephritic failure through a decrease in PTH concentrations24. If there is marked hypercalcaemias based on measuring of ionised Ca attention should be taken to govern out other causes of hypercalcaemia.
Hypokalemia may be treated with unwritten K. The exact dosage is dependent on the response to therapy, determined by supervising plasma K concentrations. Many of the commercial nephritic diets contain potassium supplementation to assistance in the intervention of hypokalemia15.
Management of anaemia in chronic nephritic disease should include an initial appraisal of the cat to govern out and handle other possible causes of anaemia. Nutritional and Fe lacks will impair the erythropoietic potency, and should be corrected prior to originating other intervention. Blood transfusions and recombinant erythropoietin therapy have all been used to handle the anaemia of chronic nephritic disease1,5,8. Recombinant human erythropoietin ( rHuEPO ) is the most effectual therapy and should be started merely if clinical marks associating to the anaemia are present, which is normally when the PCV & lt ; 18 % 25,26. There are many published doses and governments to intervention available in the literature and available by clinical experience. This is non a benign therapy as serious side effects are possible. Adverse effects of rHuEPO include polycythemia, ictuss, hypersensitivity reactions and systemic high blood pressure. Absolute failure to react to rHuEPO therapy is normally due to press lack and therefore Fe supplementation ( Fe dextran ) should be given with rHuEPO. After initial response, many cats develop antibodies to rHuEPO, which leads to a terrible furnace lining anaemia greater than that present prior to intervention. This anaemia is normally reversible when therapy is discontinued, but may non be if the cat ‘s immune system begins to aim its ain endogenous erythropoietin5. Unfortunately, research in the harvest home and selling of a felid particular erythropoietin has been unsuccessful25,26.
Treatment of systemic high blood pressure is normally carried out on a test footing, supervising for a lessening in blood force per unit area without inauspicious effects or the development of hypotension. By and large a period of approximately 2 hebdomads is sufficient to document a response. If terrible clinical marks are present, therapy may necessitate to be more aggressive. Classically, a staged curative response is recommended, get downing with dietetic Na limitation, followed by the usage of assorted pharmacological agents. The current intervention of pick for the cat is amlodipine besylate. An initial dosage of 0.625 mg/cat PO q24h is recommended and may be increased carefully if the response is hapless, to 1.25 milligrams daily. Combination therapy is required in some instances, with add-on of an ACE inhibitor or beta blocker 27.
Anorexia is normally associated with moderate to severe uraemia, and contributes to farther uraemia by ensuing in katabolism of tissue protein for energy. It may be indicated to establish therapy with appetite stimulations to assist relieve the anorexia. Recommended agents at this clip include mirtazapine and cyprohepatadine, Valium should be avoided due to the hazard of acute hepatic failure in cats1,5.
Gastric hyperacidity ensuing from hypergastrinemia may be controlled with H2 receptor antagonists7 such as Pepcid ( 0.5-1 mg/kg PO q24h ) or Zantac and a stomachic mucosal protectant such as Carafate ( 250 mg/cat q8-12h, on an empty tummy ) 1,5. Doses may necessitate to be modified in those agents excreted by the kidneys.
Treatment – Surgical Intervention
Management of end-stage nephritic disease by nephritic organ transplant therapy is by and large prohibitory because of cost, proficient, and ethical considerations, but its handiness should still be mentioned to clients wishing to prosecute all intervention avenues.
Chronic nephritic disease tends to be progressive and the long-run forecast is hapless, although with careful direction and client conformity some cats will populate a good quality of life for months to old ages.
Since the bulk of instances of chronic nephritic disease are of unknown primary cause, there are presently no preventive recommendations. Some things to see when handling the feline patient include avoiding any possible renal abuses, peculiarly in cats with preexistent via media or nephritic map or nephritic perfusion. For illustration, avoid utilizing NSAIDs ( non-steroidal anti-inflammatory drugs ) in dehydrated cats, and use endovenous fluids prior to initiation of anaesthesia and during surgery, to keep nephritic perfusion. It is of import to observe that minor nephritic abuses may total to do clinically important nephritic harm. Promptly and suitably handling conditions doing decreased nephritic perfusion including desiccation, daze and hypotension are paramount, as pre-renal and post-renal uremia, if non corrected, may take to nephritic harm and nephritic failure.
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- Hostutler RA, DiBartola SP, Chew DJ, et.al: Comparison of the effects of day-to-day and intermittent dosage calcitriol on serum parathyroid endocrine and ionised Ca concentrations in normal cats and cats with chronic nephritic failure. J Vet Intern Med 20: 1307-13, 2006.
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