Congenital polycystic kidney disease in lambs

AIM: To describe the pathology and inheritance of a congenital polycystic kidney disease (PKD) of sheep. METHODS: Mode of inheritance of PKD was investigated by evaluation of results of the disorder from planned matings in two consecutive years within subsets of a flock that had a high prevalence of PKD in lambs. Gross pathological and histopathological studies were based on tissues derived from this study. Haematoxylin and eosin (H&E)-stained paraffin sections of kidney, liver, extrahepatic biliary and pancreatic ducts, pancreas and epididymis were used to describe the lesions. RESULTS: Twenty-five lambs affected by PKD, of both sexes, were born, numbers in accord with those expected for an autosomal recessive disorder in the population studied. In all cases for which tissues were available, the renal, bile ductal (intrahepatic and extrahepatic), pancreatic and epididymal tissues had widespread dysplastic changes and associated cyst formation. CONCLUSIONS: The findings of renal cysts in conjunction with cysts in other organs are unifying features in many of the human and animal forms of PKD and suggest a related pathogenic and genetic base consistent with an autosomal recessive disorder.     

Prevalence of autosomal dominant polycystic kidney disease in Persian cats and related-breeds in Sydney and Brisbane

OBJECTIVE: A form of autosomal dominant polycystic kidney disease has been identified in Persian cats and related breeds. Two features make elimination of this disease from future generations an achievable goal: the autosomal dominant mode of inheritance and the availability of a noninvasive technique, renal ultrasonography, to identify affected cats. The aims of this study were; to determine the prevalence of the disease in Persian cats and related breeds in Sydney and Brisbane, to determine any effect of domicile and breed on disease prevalence, to alert veterinary practitioners to the prevalence of autosomal dominant polycystic kidney disease and to propose methods of eliminating the disease from future generations of cattery-bred cats. DESIGN: To be included in this scheme, cats had to be of Persian or related breed and be older than 10 months-of-age. Younger cats were excluded because of the increased likelihood of a false negative result. Renal ultrasonography was performed using either a Medison 600 with a 7.5 MHz mechanical sector scanner (n = 228, Brisbane) or using an ATL UltraMark-9 with a 5 to 10 MHz linear array transducer (n = 92, Sydney). The effects of domicile (Sydney versus Brisbane) and breed on the prevalence of autosomal dominant polycystic kidney disease were tested using two-tailed Fisher's Exact tests. RESULTS: A total of 320 cats were tested comprising 230 Persians, 48 Himalayans, 17 Exotics, 14 Burmillas, 6 Ragdolls and 5 Chinchillas. The prevalence of autosomal dominant polycystic kidney disease in Sydney (45%) and Brisbane (42%) was comparable and no sex predilection was identified. The disease was not detected in Ragdolls, although only a small number was tested. Two of 14 Burmilla cats were positive (14%), demonstrating that long hair coat and brachycephalic features do not segregate with the polycystic kidney disease trait. CONCLUSION: These results show that the prevalence of autosomal dominant polycystic kidney disease amongst purebred, long-haired cats in Australia is currently very high. Ultrasound detection schemes are easy to establish and breeder participation can be encouraged through subsidisation.     

Feline polycystic kidney disease in Persian and other cats: a prospective study using ultrasonography

OBJECTIVE: To determine the prevalence of feline polycstic kidney disease in Persian cats presented to the University of Melbourne Veterinary Clinic and Hospital between February and August 1999. DESIGN: A prospective clinical study using client owned animals was performed. PROCEDURE: Two hundred and fifty Persian cats, ranging in age from 13 weeks to 10 years, were presented to the University of Melbourne Veterinary Clinic and Hospital for ultrasound examination of both kidneys. The cats were placed in dorsal and lateral recumbency and alcohol and ultrasonic coupling gel were applied to the skin. The kidneys were examined ultrasonographically in longitudinal, sagittal and transverse planes. Results were recorded for each cat at the time of examination as either negative or positive for PKD. In addition 14 Exotics (short-haired Persians), 4 Ragdolls and 3 British Short-Hair cats were examined. RESULTS: Forty five percent of Persian cats examined were found to be positive for feline polycystic kidney disease on the basis of presence of anechoic cysts within the renal parenchyma. These cats ranged in age from 13 weeks to 10 years. Fifty per cent of the Exotic cats were positive for polycystic kidney disease whereas all Ragdolls and British Short Hairs were negative for the disease. Only one positive cat was reported to be showing clinical signs of renal disease. CONCLUSION: The prevalence of feline polycstic disease in Persian cats presented to the University of Melbourne between February and August 1999 was 45%. Exotic cats were found to have the slightly higher incidence of 50%.     

Congenital dilatation of the bile ducts (Caroli's disease) in young dogs

We describe 8 young dogs with congenital dilatation of the intra- and extrahepatic bile ducts and diffuse cystic kidney disease, compatible with Caroli's disease in humans. The dogs were referred between 1980 and 2000 because of chronic disease at an age of 6 months to 3 years. These dogs included 3 Collies, 2 Frisian Stabyhouns, 2 Jack Russell Terriers, and 1 mixed-breed dog. The most common signs were vomiting (6/6), polyuria and polydipsia (4/6), and anorexia (4/6). Ascites was a common finding (4/6). Clinicopathologic abnormalities were available for 6 dogs. All had increased plasma alkaline phosphatase activity and fasting bile acids: increased alanine aminotransferase activity and urea and creatinine concentrations were present in 50% of dogs. Ultrasound examination of the liver showed severely dilated bile ducts without evidence of obstruction, and calcification in all cases but 1. Postmortem examination revealed severe dilatation of the larger intra- and extrahepatic bile ducts. The common bile duct and gall bladder were normal, and the bile system was patent. The ducts contained a clear viscid fluid often with calcified material. Microscopically, marked portal fibrosis was present, often with abnormally structured dilated bile ducts lined with columnar or cuboid epithelium and regularly small calcifications. The lesion was complicated by ascending cholangitis in 1 dog. The kidneys showed marked cortical and medullary fibrosis with a diffuse radial cystic pattern; only slight renal fibrosis was found in the oldest dog. Seven dogs were euthanized without treatment; the oldest dog was alive and well 5 months after diagnosis and was maintained on a protein-restricted diet.     

Polycystic kidney disease in bull terriers: an autosomal dominant inherited disorder

The prevalence, mode of inheritance and urinalysis findings in Bull Terriers with polycystic kidney disease were assessed by screening 150 clinically normal dogs. The disorder was diagnosed in 39 dogs on the basis of renal ultrasound results and family history of the disease. In equivocal cases confirmation required gross and histopathological renal examination. Necropsy was performed on nine affected dogs and the kidneys from another five affected animals were also examined. Renal cysts were usually bilateral, occurred in cortex and medulla and varied from less than 1 mm to over 2.5 cm in diameter. Cysts were lined by epithelial cells of nephron origin. Abnormal urine sediment and proteinuria were common in affected dogs. The disease appears to be inherited in a highly penetrant autosomal dominant manner.     

Identification of feline polycystic kidney disease mutation using fret probes and melting curve analysis

We developed and validated a real-time polymerase chain reaction (PCR) assay using fluorescent hybridization probes and melting curve analysis to identify the PKD1 exon 29 (C → A) mutation, which is implicated in polycystic kidney disease of cats. DNA was isolated from peripheral blood of 20 Persian cats. The employ of the new real-time PCR and melting curve analysis in these samples indicated that 13 cats (65%) were wild type homozygotes and seven cats (35%) were heterozygotes. Both PCR-RFLP and sequencing procedures were in full agreement with real-time PCR test results. Sequence analysis showed that the mutant gene had the expected base change compared to the wild type gene.The new procedure is not only very reliable but also faster than the techniques currently applied for diagnosis of the mutation.     

Arterial blood gas anomaly in canine hepatobiliary disease

Arterial blood gas analysis is an important diagnostic and monitoring tool for respiratory abnormalities. In human medicine, lung complications often occur as a result of liver disease. Although pulmonary complications of liver disease have not been reported in dogs, we have frequently encountered hypoxemia in dogs with liver disorders, especially extrahepatic biliary obstruction. In addition, respiratory disorders account for 20% of perioperative fatalities in dogs. Therefore, in this study, we evaluated the respiratory status in dogs with hepatobiliary disease by arterial blood gas analysis. PaO₂ and PaCO₂ were measured. Alveolar-arterial oxygen difference (AaDO₂), the indicator of gas exchange efficiency, was calculated. Compared to healthy dogs (control group), hepatobiliary disease dogs had significantly lower PaO₂ and higher AaDO₂. Hypoxemia (PaO₂ of ≤80 mmHg) was observed in 28/71 dogs with hepatobiliary disease. AaDO₂ was higher (≥30 mmHg) than the control group range (11.6 to 26.4 mmHg) in 32/71 hepatobiliary disease dogs. By classifying type of hepatobiliary disease, dogs with extrahepatic biliary obstruction and chronic hepatitis showed significantly lower PaO₂ and higher AaDO₂ than in a control group. Dogs with chronic hepatitis also had significantly lower PaCO₂. The present study shows that dogs with hepatobiliary disease have respiratory abnormalities more than healthy dogs. Preanesthetic or routine arterial blood gas analysis is likely beneficial to detect the respiratory abnormalities in dogs with hepatobiliary disease, especially extrahepatic biliary obstruction and chronic hepatitis.     

Congenital hypoplasia of the dorsal colon in a Quarter Horse filly with chronic,intermittent colic

Congenital colonic anomalies are rare in the horse and, to the authors' knowledge, no cases have been reported that include measurements of each segment of the large colon to confirm which section is abnormal. This case report describes chronic, intermittent colic in a Quarter Horse filly that had been attributed to chronic idiopathic hepatitis prior to an exploratory laparotomy. A colonic anomaly discovered at surgery became the primary differential for aetiology of the intermittent colic. Euthanasia of the filly and necropsy allowed further examination of the anomaly, where it was determined that the dorsal colon was short compared to the ventral large colon. In addition, the diagnosis of chronic idiopathic hepatitis was confirmed.     

Absence of renal cortical anisotropic backscattering artifact in feline chronic kidney disease

Renal cortical anisotropy backscattering artifact (CABA) is a focal hyperechoic region where the tubules are parallel to the incident ultrasound beam, reflecting most of the beams to the transducer. To investigate the association between chronic kidney disease (CKD) and the absence of renal CABA in cats. Ultrasonographic renal images of 40 cats with CKD (stage II-IV) and 36 clinically healthy cats were blindly evaluated by two observers to determine the visibility of renal CABA. Inter- and intraobserver agreements were evaluated using McNemar’s test. The association between the absence of renal CABA and CKD was assessed using Fisher’s exact test. Excellent intraobserver and substantial interobserver agreements were demonstrated. A significant association (P < .0001) between absent renal CABA and CKD stage was revealed in all cats. Cats with CKD had an increased risk of the absence of renal CABA (Odds ratio, 56.0; 95% CI, 13.8–227.0) compared with the clinically healthy cats. The absence of renal CABA revealed 87.5% sensitivity and 88.9% specificity to detect CKD in all cats, and 91.7% sensitivity and 83.3% specificity in aged cats. Our study demonstrated a correlation between feline CKD and the absence of renal CABA, providing a feasible and alternative method for feline CKD evaluation.     

Comparative study of chronic kidney disease in dogs and cats: Induction of myofibroblasts

We investigated the kidneys of dogs and cats to clarify whether renal myofibroblasts induction is associated with the severity of chronic kidney disease (CKD). Immunohistochemical expression of myofibroblast markers, α-smooth muscle actin (SMA) and vimentin, were evaluated quantitatively. The degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration, and interstitial fibrosis were also evaluated quantitatively. The plasma creatinine (pCre) concentrations correlated with glomerulosclerosis, cell infiltration, and fibrosis in dogs, and only with fibrosis in cats. The α-SMA expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, and with pCre and fibrosis in cats. Tubular vimentin expression correlated with fibrosis in cats, but not in dogs. Interstitial vimentin expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, but only with pCre in cats. In conclusion, it was suggested that the severity of CKD in dogs and cats was mediated by different pathways associated with myofibroblasts expression.     

Survival in cats with naturally occurring chronic kidney disease (2000-2002)

Background: Duration of survival of cats with naturally occurring chronic kidney disease (CKD) is poorly characterized.
Hypothesis: Stage of kidney disease based on serum creatinine concentration (SCr) at the time of diagnosis and after correction of prerenal azotemia is strongly associated with duration of survival in cats.
Animals: Two hundred and eleven client-owned cats with naturally occurring CKD evaluated between April 2000 and January 2002.
Methods: Retrospective case review of 733 cats with SCr > 2.3 mg/dL. Examination of the medical records identified 211 cats that met all other inclusion and exclusion criteria for this study. Clinical characteristics, clinicopathologic data, and survival times were extracted from the medical record. Owners and referring veterinarians were contacted by phone to obtain follow-up if it was not documented in the record. Kaplan-Meier survival curves were performed to determine survival times for International Renal Interest Society (IRIS) stage both at diagnosis and at baseline (ie, after correction of prerenal azotemia).
Results: Median survival for cats in IRIS stage IIb at the time of diagnosis was 1,151 days (range 2–3,107), and was longer than survival in stage III (median 778, range 22–2,100) or stage IV (median 103, range 1–1,920) ( P -value < .0001). P -value for effect of stage at diagnosis was <.0001.
Conclusions and Clinical Importance: IRIS stage of CKD based on serum creatinine at the time of diagnosis is strongly predictive of survival in cats with naturally occurring CKD.     

Iron status and erythropoiesis response to darbepoetin alfa in dogs with chronic kidney disease

Iron metabolism, hepcidin and some blood profiles were investigated in 13 healthy and 31 chronic kidney disease (CKD) dogs. The study consisted of 2 experiments, experiment I included healthy dogs (CONT) and CKD dogs (stage 2, 3 and 4), while experiment II consisted of anemic CKD dogs subjected to 28-day darbepoetin alfa treatment. The response to darbepoetin alfa could divide anemic CKD dogs into responder (RP) and non-responder (NRP) subgroups. The results from experiment I showed that packed cell volume (PCV) and plasma albumin concentration were significantly lower in CKD dogs of all stages while the total iron binding capacity (TIBC) was lower in only CKD stage 3 and 4 compared with dogs in CONT group. The PCV was related to both TIBC and albumin when considering among all dogs or only in CKD dogs. The hepcidin concentration in CKD dogs with anemia was lower than those without anemia (P<0.05). In experiment II before darbepoetin alfa treatment, RP subgroup had significantly higher iron and TIBC compared with NRP subgroup (P<0.05), the iron concentration was decreased only in RP subgroup after darbepoetin alfa treatment (P<0.05). The percent increase in PCV was correlated with initial TIBC (P<0.01). Plasma hepcidin concentration was not different between CONT and CKD groups and between RP and NRP subgroups both before and after darbepoetin alfa treatment. It is concluded that TIBC and plasma iron concentration play role on anemia and erythropoietic response to darbepoetin alfa treatment in CKD dogs.     

Evaluation of albuminuria and its relationship with blood pressure in dogs with chronic kidney disease

Background: Microalbuminuria and hypertension have long been associated with a guarded prognosis in human patients with a variety of diseases. In veterinary medicine, tests for microalbuminuria have been used for detecting early kidney damage, but there is little information regarding its association with high blood pressure in dogs with chronic kidney disease (CKD). Objective: The objective of this study was to evaluate albuminuria and its association with arterial hypertension in dogs with CKD. Methods: Urinary albumin:creatinine (UAC) ratio, urinary protein:creatinine (UPC) ratio, and systolic blood pressure were determined in 39 clinically healthy dogs and 40 dogs with CKD. Results: UAC in dogs with CKD (range, 0.002–7.99; median, 0.38) was statistically different from that of control dogs (range, 0.0005–0.01; median, 0.002). Microalbuminuria (UAC 0.03–0.3) and macroalbuminuria (UAC>0.3) were detected in 32.5% and 50% of dogs with CKD, respectively. Sixty percent (24/40) of dogs with CKD had systolic pressure ≥180 mmHg; in these dogs, UAC ratio (range, 0.006–7.99; median, 1.72) was significantly higher than in dogs with CKD and systolic pressure<180 mmHg (range, 0.002–4.83; median, 0.10). Of hypertensive dogs with CKD, those with UPC>1.0 usually had macroalbuminuria, those with UPC 0.5–1.0 usually had microalbuminuria, and those with UPC<0.5 usually lacked albuminuria. Conclusions: UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests designed to detect microalbuminuria may be useful for hypertensive dogs with CKD and a UPC≤1.0 to detect the onset and magnitude of albuminuria. Once macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.     

Congenital nutritional myodegeneration (white muscle disease) in a red deer (Cervus elaphus) calf

CASE HISTORY A 5-day-old red deer calf was submitted with tachypnoea and dyspnoea, and was reluctant to move.

CLINICAL FINDINGS: Muscular damage was established via elevated creatinine phosphokinase (CPK) activities (5,000 U/L), while concentrations of Se in whole blood were low (24.8 nmol/L). The animal died despite treatment with penicillin-streptomycin and 0.1 mg/kg Se/vitamin E administered by S/C injection.

DIAGNOSIS: Necropsy and histological examination of cardiac and skeletal muscle confirmed the presumptive diagnosis of congenital white muscle disease (WMD). Prophylactic administration of a Se/vitamin E commercial preparation (as above) to another calf born in the same herd one month later was associated with good health and apparently normal growth and development.

CLINICAL RELEVANCE: Congenital WMD due to Se deficiency can be fatal in red deer calves. However, prophylactic administration of Se and vitamin E to neonatal calves may be beneficial for neonatal red deer calves.     

Relationship of glomerular filtration rate based on serum iodixanol clearance to IRIS staging in cats with chronic kidney disease

We examined the correlation between the glomerular filtration rate (GFR) estimated from an equation based on the serum iodixanol clearance technique and International Renal Interest Society (IRIS) stages of chronic kidney disease (CKD) in cats. The equation included the injection dose, sampling time, serum concentration and estimated volume of distribution (Vd) of the isotonic, nonionic, contrast medium iodixanol as a test tracer. The percent changes in the median basal GFR values calculated from the equation in CKD cats resembled those of IRIS stages 1–3. These data validate the association between the GFR derived from the simplified equation and IRIS stages based on the serum creatinine concentration in cats with CKD. They describe the GFR ranges determined using single-sample iodixanol clearance for healthy cats and cats with various IRIS stages of CKD.     

Positive correlation between renal tubular flattening and renal tubular injury/interstitial fibrosis in murine kidney disease models

The number of patients with chronic kidney disease (CKD) is growing continuously globally. In order to study pathogenesis and mechanisms, many animal models have been developed, including spontaneous, genetic, and induced models. Although each type of CKD shows disease-specific tissue changes in the early stages, tubular disorder and interstitial fibrosis histologically occur in the course of progression to end-stage renal failure. Therefore, the quantification of tubular disorder and interstitial fibrosis in CKD research using animal models is essential for measuring the degree of CKD severity and, thus, efficacy of therapeutic agents. Several strategies have been used to quantify interstitial fibrosis. Among scoring factors, renal tubular flattening can be quantitatively evaluated easily and inexpensively. However, the diagnostic value of renal tubular flattening evaluation has not been investigated previously. Therefore, in this study, we investigated the correlation between renal tubular flattening and interstitial fibrosis or renal tubular injury markers. We observed a strong correlation between the degree of tubular injury/interstitial fibrosis and renal tubular flattening in three types of mouse renal disease model. This is advantageous because rapidly advancing technologies such as artificial intelligence and image processing can be easily applied; hence, a more precise, objective, and quantitative diagnosis should be possible in the future.     

Aldosterone and the mineralocorticoid receptor in renal injury: A potential therapeutic target in feline chronic kidney disease

There is a growing body of experimental and clinical evidence supporting mineralocorticoid receptor (MR) activation as a powerful mediator of renal damage in laboratory animals and humans. Multiple pathophysiological mechanisms are proposed, with the strongest evidence supporting aldosterone-induced vasculopathy, exacerbation of oxidative stress and inflammation, and increased growth factor signalling promoting fibroblast proliferation and deranged extracellular matrix homeostasis. Further involvement of the MR is supported by extensive animal model experiments where MR antagonists (such as spironolactone and eplerenone) abrogate renal injury, including ischaemia-induced damage. Additionally, clinical trials have shown MR antagonists to be beneficial in human chronic kidney disease (CKD) in terms of reducing proteinuria and cardiovascular events, though current studies have not evaluated primary end points which allow conclusions to made about whether MR antagonists reduce mortality or slow CKD progression. Although differences between human and feline CKD exist, feline CKD shares many characteristics with human disease including tubulointerstitial fibrosis. This review evaluates the evidence for the role of the MR in renal injury and summarizes the literature concerning aldosterone in feline CKD. MR antagonists may represent a promising therapeutic strategy in feline CKD.     

A longitudinal study on the acceptance and effects of a therapeutic renal food in pet dogs with IRIS‐Stage 1 chronic kidney disease

Currently, nutritional management is recommended when serum creatinine (Cr) exceeds 1.4 mg/dl in dogs with IRIS‐Stage 2 chronic kidney disease (CKD) to slow progressive loss of kidney function, reduce clinical and biochemical consequences of CKD, and maintain adequate nutrition. It is unknown if dietary interventions benefit non‐azotemic dogs at earlier stages. A prospective 12‐month feeding trial was performed in client‐owned dogs with IRIS‐Stage 1 CKD (n = 36; 20 had persistently dilute urine with urine specific gravity (USG) <1.020 without identifiable non‐renal cause; six had persistent proteinuria of renal origin with urine protein creatinine (UPC) ratio >0.5; 10 had both). Ease of transition to therapeutic renal food and effects on renal biomarkers and quality of life attributes were assessed. Dogs were transitioned over 1 week from grocery‐branded foods to renal food. At 0, 3, 6, 9, and 12‐months a questionnaire to assess owner's perception of their pet's acceptance of renal food and quality of life was completed. Renal biomarkers, including serum Cr, blood urea nitrogen (BUN), and symmetric dimethylarginine (SDMA), and USG and UPC ratio were measured. Of 36 dogs initially enrolled, 35 (97%) dogs were transitioned to therapeutic renal food. Dogs moderately or extremely liked the food 88% of the time, ate most or all of the food 84% of the time, and were moderately or extremely enthusiastic while eating 76% of the time. All renal biomarkers (Cr, BUN, and SDMA) were decreased (p ≤ .05) from baseline at 3‐months, and remained decreased from baseline at 12‐months in dogs completing the study (n = 20). Proteinuria was reduced in 12 of 16 dogs (p = .045) with proteinuria. Owners reported improvement in overall health and quality of life attributes, and hair and coat quality (all p < .01). In summary, dogs with IRIS‐Stage 1 CKD readily transition to renal food. Decreasing serum biomarker concentrations and reduction in proteinuria suggest stabilized kidney function.