Chronic Renal Failure-Causes, Clinical Findings, Treatments and Prognosis.

Chronic kidney disease (CKD) is rare in horses with an overall prevalence reported to be 0.12%. There is often a continuum from Acute Kidney Injury (AKI) to CKD, and patients with CKD may be predisposed to episodes of AKI. The most common clinical signs are non-specific with weight loss, polyuria/polydipsia and ventral edema. Less common clinical signs are poor appetite and performance, dull hair coat, oral ulcerations, gastro-intestinal ulceration, gingivitis, dental tartar and diarrhea. Rarely, horses may develop forebrain signs. Creatinine increases when at least 2/3 of kidney function have been lost and a more accurate assessment of kidney function is an estimated glomerular filtration rate measuring iohexol clearance time combined with protein content in the urine. Tubulointerstitial disease and glomerulonephritis are common causes of chronic kidney disease together with pyelonephritis and nephrolithiasis. Dietary changes and avoiding nephrotoxic drugs are key in slowing down the degenerative process.

A Carrel patch technique for renal transplantation in cats.

OBJECTIVE: To evaluate the feasibility of a Carrel patch method in feline renal transplantation. STUDY DESIGN: Descriptive case series. ANIMALS: Nine healthy donor cats and 9 client recipient cats with chronic renal failure. METHODS: Renal transplantation was performed in 9 cats with chronic renal failure after collection of a donor's left kidney with a Carrel patch technique. A patch of donor aortic wall was removed with either 2 or 1 renal artery (ies) (n = 1 and 8 cats, respectively) central to the patch, with a cuff of tissue (≤1 mm) protruding from the base of the vessels. The Carrel patch was implanted in recipient cats with an end-to-side artery-to-aorta anastomosis, in a simple-continuous pattern of 9-0 nylon. The renal vein and ureter were implanted as previously described. RESULTS: All donors and recipients survived surgery without vascular complication. CONCLUSION: The Carrel patch is a novel approach allowing the harvest of kidneys with multiple renal arteries. The technique also simplified the implant procedure, potentially decreasing the risks of bleeding and thrombosis.

Other Risks/Possible Benefits of Obesity.

Obesity is not a cosmetic or social issue; it is an animal health issue. The metabolic effects of obesity on insulin resistance and development of hyperlipidemia and the mechanical stress excess weight places on the musculoskeletal system are well established in the literature. Additional health risks from obesity, such as fatty accumulation in the liver, intestinal bacterial dysbiosis, and changes to renal architecture, are less well understood, but have been demonstrated to occur clinically in obese animals and may lead to deleterious long-term health effects. Keeping dogs and cats lean lowers their risk for development of certain diseases and leads to a longer and better quality of life.

Ureteral Papilla Implantation as a Technique for Neoureterocystostomy in Cats Undergoing Renal Transplantation: 30 Cases.

OBJECTIVE: To describe the clinical outcome of donor and recipient cats undergoing ureteral papilla harvest and implantation as a technique for neoureterocystostomy in clinical kidney transplant. STUDY DESIGN: Retrospective case series. ANIMALS: Donor (n=31) and recipient (n=30) cats that underwent kidney harvest and transplantation using ureteral papilla implantation technique for neoureterocystostomy. METHODS: Medical records for donor and recipient cats presented to the University of Wisconsin Veterinary Teaching Hospital from January 2003 to December 2014 were reviewed. Data recorded included complete blood count, serum chemistry panel, surgical technique, diagnostic imaging results, short- and long-term complications, and anesthetic survival. RESULTS: All 30 recipients recovered from anesthesia. Four died within 24 hours and 26 survived to hospital discharge. Serum creatinine was within the reference interval by 72 hours in 22/26 cats (85%). Complications related to the ureteral papilla implantation technique were seen in only 1 cat (3%). Uroabdomen diagnosed on day 3 ultimately resolved over the following 24 hours without surgical intervention. All 31 donor cats survived to discharge. Four donors (13%) experienced mild, transiently increased serum creatinine. CONCLUSION: Ureteral papilla implantation is a viable technique for neoureterocystostomy in cats undergoing kidney transplantation. Proposed benefits for the recipient include a less technically challenging anastomosis, decreased risk of ureteral obstruction at the anastomosis site, and reduced risk of leakage compared to previous reports. Benefits for recipients should be weighed against risks to donors, including a more complex ureteral harvest, increased surgical time, and potential injury or obstruction of the contralateral ureteral papilla.

Detection of indoxyl sulfate levels in dogs and cats suffering from naturally occurring kidney diseases.

Indoxyl sulfate (IS), a protein-bound uraemic toxin, has been found to accumulate in the serum of people with renal diseases and is associated with free radical induction, nephrotoxicity cardiovascular toxicity, and osteoblast cytotoxicity. Although IS has been studied in humans and in experimental models, the role of IS in dogs and cats with kidney disease has not been investigated. A high performance liquid chromatography system was applied to detect plasma IS concentrations in non-azotaemic animals (63 dogs, 16 cats) and in animals with renal azotaemia (66 dogs, 69 cats). The IS levels of azotaemic animals were significantly higher (P <0.01) than those of non-azotaemic animals (median [IQR] 20.4 (9.5) mg/L vs. 7.2 (8.8) mg/L for dogs; median [IQR] 21 (18.9) mg/L vs. 14.8 (12.3) mg/L for cats). The IS level was significantly correlated with blood urea nitrogen, serum creatinine and phosphate concentrations. Dogs with acute kidney injury had significantly higher IS levels (P <0.01) than those with chronic kidney diseases (CKD) (median [IQR] 57.7 (40.8) mg/L vs. 17.7 (25.1) mg/L). When CKD was graded using the International Renal Interest Society (IRIS) staging system, IS levels were correlated with CKD severity in both dogs and cats. The IS concentration is directly related to loss of renal function. Further studies are necessary to determine whether measurement of IS provides any additional diagnostic or prognostic information in dogs and cats with kidney disease.

Hyperammonaemia in four cats with renal azotaemia.

Hyperammonaemia is well reported in animals with advanced hepatic disease and portosystemic shunts, but is unreported in cats with renal disease. This case series describes four cats with severe renal azotaemia in which elevated ammonia levels were detected during the course of treatment. In two cases hyperammonaemia was detected at a time when neurological signs consistent with encephalopathy had developed. This raises the possibility that hyperammonaemia may play a role in the development of encephalopathy in cats with renal azotaemia.

Preliminary study of interaction of clarithromycin with tacrolimus in cats.

Tacrolimus (Tac) is a core immunosuppressive drug in human organ transplantation. In feline kidney transplantation, however, the cost of Tac therapy is a significant obstacle. Clarithromycin (CLM) increases the blood trough level of Tac, effectively reducing the Tac dosage in human transplant patients. The interaction between CLM and Tac in cats has not been reported. In this study, the effect of multiple CLM dosing on the pharmacokinetics of Tac in three healthy cats was investigated. The treatments included Tac at 0.3 mg/kg and Tac at 0.3 mg/kg + multiple-dose CLM at 10 mg/kg. Co-administration of CLM and Tac resulted in significant increases in the oral bioavailability of Tac. These preliminary findings suggest that administration of multiple doses of CLM may decrease the required Tac dosage in Tac-based immunosuppressive therapy used as an alternative to the classic cyclosporine-based protocol for feline renal transplantation.

A retrospective study of end-stage renal disease in captive polar bears (Ursus maritimus).

This retrospective study summarizes 11 cases of end-stage renal disease (ESRD) in captive polar bears (Ursus maritimus) from eight zoologic institutions across the United States and Canada. Ten bears were female, one was male, and the mean age at the time of death was 24 yr old. The most common clinical signs were lethargy, inappetence, and polyuria-polydipsia. Biochemical findings included azotemia, anemia, hyperphosphatemia, and isosthenuria. Histologic examination commonly showed glomerulonephropathies and interstitial fibrosis. Based on submissions to a private diagnostic institution over a 16-yr period, ESRD was the most commonly diagnosed cause of death or euthanasia in captive polar bears in the United States, with an estimated prevalence of over 20%. Further research is needed to discern the etiology of this apparently common disease of captive polar bears.

Association between excess body weight and urine protein concentration in healthy dogs.

BACKGROUND: Markedly overweight people can develop progressive proteinuria and kidney failure secondary to obesity-related glomerulopathy (ORG). Glomerular lesions in dogs with experimentally induced obesity are similar to those in people with ORG. OBJECTIVES: The aim of this study was to evaluate if urine protein and albumin excretion is greater in overweight and obese dogs than in dogs of ideal body condition. METHODS: Client-owned dogs were screened for underlying health conditions. These dogs were assigned a body condition score (BCS) using a 9-point scoring system. Dogs with a BCS of ≥ 6 were classified as being overweight/obese, and dogs with a BCS of 4 or 5 were classified as being of ideal body weight. The urine protein:creatinine ratio (UPC) and urine albumin:creatinine ratio (UAC) were then determined, and compared between 20 overweight/obese dogs and 22 ideal body weight control dogs. RESULTS: Median UPC (0.04 [range, 0.01-0.14; interquartile range, 0.07]) and UAC (0.41 [0-10.39; 3.21]) of overweight/obese dogs were not significantly different from median UPC (0.04 [0.01-0.32; 0.07]) and UAC (0.18 [0-7.04; 1.75]) in ideal body weight dogs. CONCLUSIONS: Clinicopathologic abnormalities consistent with ORG were absent from overweight/obese dogs in this study.

Serum intact parathyroid hormone levels in cats with chronic kidney disease / Avaliação das concentrações séricas de paratormônio intacto em gatos com doença renal crônica

Chronic kidney disease (CKD) is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT) is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS) as Stage II (n=12), Stage III (n=22) and Stage IV (n=6). Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH) concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved.

A doença renal crônica (DRC) em gatos é frequentemente observada e caracteriza-se como alteração multissistêmica, causada por alterações metabólicas, e o hiperparatireoidismo secundário renal (HPTSR) seria o mais comum e usualmente está associada com progressão da doença renal e mau prognóstico. Esse estudo teve como objetivo determinar a frequência do HPTSR, e discutir os possíveis mecanismos que podem contribuir para o desenvolvimento de SRHPT em gatos em diferentes estágios de DRC, pela avaliação do metabolismo do cálcio e fósforo, bem como do equilíbrio ácido-base. Quarenta gatos com DRC foram divididos em três subgrupos, de acordo com a classificação proposta pela International Renal Interest Society (IRIS), Estágio II (n=12), Estágio III (n=22) e Estágio IV (n=6). O grupo-controle foi composto por 21 gatos clinicamente saudáveis. O aumento das concentrações séricas de paratormônio intacto (PTHi) foi observado na maioria dos casos, mas principalmente no Estágio IV, no qual a hiperfosfatemia e a hipocalcemia ionizada parecem estar associadas ao desenvolvimento do HPTSR. No entanto, nos Estágios II e III, observou-se hipercalcemia ionizada, sugerindo que, nestes estágios, o desenvolvimento do HPTSR possa estar associado a outros fatores, e a acidose metabólica pode estar envolvida com o desenvolvimento de hipercalcemia ionizada. Assim, outros fatores, além da hiperfosfatemia e da hipocalcemia ionizada, possam estar envolvidos com o desenvolvimento do HPTSR, principalmente nos estágios iniciais da DRC. Futuros estudos são necessários para uma melhor compreensão da fisiopatologia do HPTSR em gatos.

Effect of weight loss in obese dogs on indicators of renal function or disease.

BACKGROUND: Obesity is a common medical disorder in dogs, and can predispose to a number of diseases. Human obesity is a risk factor for the development and progression of chronic kidney disease. OBJECTIVES: To investigate the possible association of weight loss on plasma and renal biomarkers of kidney health. ANIMALS: Thirty-seven obese dogs that lost weight were included in the study. METHODS: Prospective observational study. Three novel biomarkers of renal functional impairment, disease, or both (homocysteine, cystatin C, and clusterin), in addition to traditional markers of chronic renal failure (serum urea and creatinine, urine specific gravity [USG], urine protein-creatinine ratio [UPCR], and urine albumin corrected by creatinine [UAC]) before and after weight loss in dogs with naturally occurring obesity were investigated. RESULTS: Urea (P = .043) and USG (P = .012) were both greater after weight loss than before loss, whilst UPCR, UAC, and creatinine were less after weight loss (P = .032, P = .006, and P = .026, respectively). Homocysteine (P < .001), cystatin C (P < .001) and clusterin (P < .001) all decreased upon weight loss. Multiple linear regression analysis revealed associations between percentage weight loss (greater weight loss, more lean tissue loss; r = -0.67, r(2) = 0.45, P < .001) and before-loss plasma clusterin concentration (greater clusterin, more lean tissue loss; r = 0.48, r(2) = 0.23, P = .003). CONCLUSION AND CLINICAL IMPORTANCE: These results suggest possible subclinical alterations in renal function in canine obesity, which improve with weight loss. Further work is required to determine the nature of these alterations and, most notably, the reason for the association between before loss plasma clusterin and subsequent lean tissue loss during weight management.

Bilateral ureteropelvic junction stenosis causing hydronephrosis and renal failure in an adult cat.

A 3.5-year-old male neutered cat was presented for investigation of renomegaly appreciated during a routine physical examination. Marked renomegaly due to bilateral hydronephrosis was detected and further testing identified International Renal Interest Society stage 2, non-hypertensive, non-proteinuric chronic kidney disease. Ten months later the cat was evaluated for acute lethargy; severe azotemia with oliguria was documented. Medical therapy failed to result in clinical improvement and the cat was euthanased. Necropsy revealed bilateral marked hydronephrosis secondary to a tortuous proximal ureter consistent with proximal ureteropelvic junction stenosis. This is the first report of this disorder leading to progressive renal failure in a cat.

Pulmonary abnormalities in dogs with renal azotemia.

BACKGROUND: Clinical signs associated with respiratory tract disease are regularly encountered in people with kidney failure, and have been anecdotally reported in dogs. OBJECTIVES: To compare clinical signs indicative of pulmonary disease, clinicopathologic findings, radiographic abnormalities, and histologic findings in dogs with acute kidney injury (AKI) or International Renal Interest Society Stage 3 or 4 chronic kidney disease (CKD) to nonazotemic dogs. To determine associations between abnormalities indicative of pulmonary disease and outcome in azotemic dogs. ANIMALS: One hundred sixty-seven pet dogs (54 AKI dogs, 50 CKD dogs, 63 nonazotemic control dogs diagnosed with intracranial disease). METHODS: Retrospective cohort study comparing signalment, clinical signs, clinicopathologic variables, prevalence, and severity of pulmonary radiographic patterns, histopathologic findings, and survival times in AKI, CKD, and control dogs. RESULTS: Clinical signs of pulmonary disease were significantly more common in AKI dogs. Prevalence of an alveolar lung pattern was greater in AKI and CKD dogs. Alveolar mineralization was the most common pulmonary histologic lesion in AKI dogs (6 of 8 dogs), with concurrent alveolar concretions or mineralization of pulmonary vessels or bronchioles noted in 1 dog each; mineralization of lung tissues was not noted in control dogs. Neither clinical signs nor presence of an alveolar pattern were associated with likelihood of survival to discharge or median number of days from discharge until death. CONCLUSIONS AND CLINICAL IMPORTANCE: Abnormalities indicative of pulmonary disease are more common in azotemic dogs than in control dogs; however, prognosis is not associated with presence of clinical or radiographic pulmonary dysfunction.

Clinical pathology interpretation in geriatric veterinary patients.

Routine monitoring of clinicopathologic data is a critical component in the management of older patients because blood and urine testing allows the veterinarian to monitor trends in laboratory parameters, which may be the early indicators of disease. Laboratory profiling often provides an objective and sensitive indicator of developing disease before obvious clinical signs or physical examination abnormalities are observed. The primary key to the power of this evaluation is that the data are collected year after year during wellness checks and are examined serially. Chronic renal failure, chronic active hepatitis, canine hyperadrenocorticism, diabetes mellitus, and feline hyperthyroidism were reviewed and expected laboratory findings are summarized.

Chronic kidney disease in dogs and cats.

Chronic kidney disease (CKD) occurs commonly in older dogs and cats. Advances in diagnostics, staging, and treatment are associated with increased quality and quantity of life. Dietary modification has been shown to increase survival and quality of life and involves more than protein restriction as diets modified for use with CKD are lower in phosphorous and sodium, potassium and B-vitamin replete, and alkalinizing, and they contain n3-fatty acids. Additionally, recognition and management of CKD-associated diseases such as systemic arterial hypertension, proteinuria, and anemia benefit patients. This article summarizes staging and management of CKD in dogs and cats.

Dilated ureters, renal dysplasia, and chronic renal failure in an African elephant (Loxodonta africana).

An ultrasonographic reproductive health examination of a 26-yr-old female African elephant (Loxodonta africana) revealed bilateral ureteral wall thickening and dilatation. On ultrasonographic examination, the bladder and both ureters were normal near the trigone; however, the cranial-most aspect of each ureter was dilated and thickened for a length of 30-50 cm. The same month, elevated blood creatinine (3.0 mg/dl), and urine protein-creatinine ratio (4.0) were observed. Chronic renal failure was diagnosed based on these abnormalities, and the persistent ureteral dilatation was seen on subsequent ultrasound examinations. Complete blood cell counts, serum chemistries, and urinalyses remained relatively unchanged until 24 mo after diagnosis, at which time azotemia, hypophosphatemia, and hypercalcemia (including elevated ionized calcium) developed. Hydronephrosis of both kidneys and prominent sacculation of the left ureter were noted on ultrasonographic examination. Lethargy, ventral edema, and oral mucosal ulceration acutely developed 30 mo after diagnosis. Although blood urea nitrogen remained elevated, creatinine, total calcium, and ionized calcium returned to within reference ranges at that time. Due to rapid clinical decline and grave prognosis, humane euthanasia was elected. Bilateral ureteral dilatation, dysplasia of the right kidney, and chronic nephritis of the left kidney were identified postmortem.

Interaction of clarithromycin with cyclosporine in cats: pharmacokinetic study and case report.

Clarithromycin (CLM) has been known to increase the cyclosporine (CsA) trough levels in human transplant patients. However, the interaction of CLM with CsA has not been reported in cats. In this study, the effects of oral dosing of CLM on the pharmacokinetics and dosing of CsA in cats were investigated. Co-administration of CLM with CsA resulted in significant increases of oral bioavailability of CsA. In addition, CLM reduced the CsA dosage required to maintain the therapeutic CsA trough levels to almost 35% of the initial CsA therapy and the dose frequency was successfully replaced from a twice a day schedule to once a day in a feline kidney transplant patient. The addition of CLM to the regular CsA-based immunosuppression could be used as an effective alternative to classical ketoconazole treatment in feline kidney transplant patients and may result in substantial cost saving and convenience for the cat owners.

The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases.

BACKGROUND: Anemia is present in 30-65% in cats with chronic kidney disease (CKD) and few long-term treatment options exist. Darbepoetin is effective in treating anemia of kidney disease in humans and may be used in cats. HYPOTHESIS/OBJECTIVE: To evaluate the use of darbepoetin, a recombinant analog of human erythropoietin, to stimulate erythropoiesis, and to effectively treat anemia of kidney disease in cats. ANIMALS: Twenty-five of 66 cats that received ≥ 2 doses of darbepoetin at the Animal Medical Center between January 2005 and December 2009 were included in this study. METHODS: Cats were included in the study if they received darbepoetin and follow-up data were available for at least 56 days and had CKD as a primary clinical diagnosis. Cats were excluded if they were treated with darbepoetin but did not have kidney disease. Response to treatment was defined as reaching or exceeding a target packed red blood cell volume or hematocrit of 25%. RESULTS: Fourteen of 25 cats responded. Thirteen of those 14 cats received a dosage of 1 µg/kg/wk or higher. Presumptive adverse effects included vomiting, hypertension, seizures, and fever. CONCLUSIONS AND CLINICAL RELEVANCE: Darbepoetin is effective for treatment of anemia of kidney disease in cats. Pure red cell aplasia appears to be less common with darbepoetin than with epoetin usage.

Evaluation of recipes for home-prepared diets for dogs and cats with chronic kidney disease.

OBJECTIVE: To evaluate recipes of diets recommended for animals with chronic kidney disease (CKD), compare nutritional profiles for those recipes to requirements for adult dogs and cats, and assess their appropriateness for the management of CKD. DESIGN: Evaluation study. SAMPLE: Recipes of 67 home-prepared diets promoted for use in dogs (n = 39 recipes) and cats (28) with CKD. PROCEDURES: Recipes were analyzed with computer software to determine calories, macronutrient calorie distribution, and micronutrient concentrations and were assessed for appropriateness for the management of CKD. RESULTS: Assumptions were required for the analysis of every recipe, and no recipe met all National Research Council nutrient recommended allowances (RA) for adult animals. Compared with RAs, concentrations of crude protein or at least 1 amino acid were low in 30 of 39 (76.9%) canine recipes and 12 of 28 (42.9%) feline recipes. Choline was most commonly below the RA in both canine (37/39 [94.9%]) and feline (23/28 [82.1%]) recipes; selenium (34/39 [87.2%] canine and 9/28 [32.1 %] feline recipes), zinc (24/39 [61.5%] canine and 19/28 [67.9%] feline recipes), and calcium (22/39 [56.4%] canine and 7/28 [25.0%] feline recipes) concentrations were also frequently below recommendations. The median phosphorus concentration in canine and feline recipes was 0.58 and 0.69 g/1,000 kcal, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Many problems with nutritional adequacy were detected, and use of the recipes could result in highly variable and often inappropriate diets. Many recipes would not meet nutritional and clinical needs of individual patients and should be used cautiously for long-term feeding.

Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is common in geriatric cats, but often appears to be stable for long periods of time. OBJECTIVES: To describe CKD progression and identify risk factors for progression in newly diagnosed azotemic cats. ANIMALS: A total of 213 cats with CKD (plasma creatinine concentration > 2 mg/dL, urine specific gravity < 1.035) were followed up until progression occurred or for at least 1 year; 132, 73, and 8 cats were in International Renal Interest Society (IRIS) stages 2, 3, and 4, respectively. METHODS: Progression was defined as a 25% increase in plasma creatinine concentration. Logistic regression was used to assess variables at diagnosis that were associated with progression within 1 year. Changes in IRIS stage during follow-up also were described. Cases that remained in stages 2 or 3, but did not have renal function assessed in the last 60 days of life, were excluded from analysis of the proportion reaching stage 4. RESULTS: Of the cats, 47% (101) progressed within 1 year of diagnosis. High plasma phosphate concentration and high urine protein-to-creatinine ratio (UPC) predicted progression in all cats. Low PCV and high UPC independently predicted progression in stage 2 cats, whereas higher plasma phosphate concentration predicted progression in stage 3 cats; 19% (18/94) of cats diagnosed in stage 2; and 63% (34/54) of cats diagnosed in stage 3 reached stage 4 before they died. CONCLUSIONS: Proteinuria, anemia, and hyperphosphatemia may reflect more progressive kidney disease. Alternatively, they may be markers for mechanisms of progression such as tubular protein overload, hypoxia, and nephrocalcinosis.