Tubulointerstitial nephritis causes decreased renal expression and urinary excretion of cauxin, a major urinary protein of the domestic cat

Cauxin, a member of mammalian carboxylesterases (EC 3.1.1.1), is excreted as a major urinary protein in the domestic cat. Urinary cauxin is derived from the kidney proximal straight tubules. Here, we report changes in the renal expression and urinary excretion of cauxin in cats with tubulointerstitial nephritis (TIN). Immunohistochemistry using anti-cauxin antibody showed fewer cauxin-positive tubules in 15 TIN cases than in normal animals. In areas with tubulointerstitial damage, fibroblasts and inflammatory cells replaced renal tubules, and cauxin-positive tubules consequently disappeared. Urine was analysed in six of the 15 cases. In the two cases with mild tubulointerstitial changes, urinary cauxin was detected using SDS-PAGE with Coomassie staining. In the four cases with severe tubulointerstitial changes, urinary cauxin was below the detection limit using Western blotting. These results indicate that the renal expression and urinary excretion of cauxin decrease with the progression of TIN in cats.     

Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984)

The historic, physical, laboratory, and histologic findings for 74 cats with chronic renal disease were reviewed. Most cats were older, and no breed or sex predilection was detected. This most common clinical signs detected by owners were lethargy, anorexia, and weight loss. Dehydration and emaciation were common physical examination findings. Common laboratory findings were nonregenerative anemia, lymphopenia, azotemia, hypercholesterolemia, metabolic acidosis, hyperphosphatemia, and isosthenuria. The most common morphologic diagnosis was chronic tubulointerstitial nephritis of unknown cause. The other pathologic diagnoses were renal lymphosarcoma, renal amyloidosis, chronic pyelonephritis, chronic glomerulonephritis, polycystic renal disease, and pyogranulomatous nephritis secondary to feline infectious peritonitis.     

Evaluation of the effects of ischemic injury and ureteral obstruction on delayed graft function in cats after renal autotransplantation

OBJECTIVE: To determine the relative importance of ischemic injury to delayed graft function (DGF) in cats. STUDY DESIGN: Experimental study. ANIMALS: Six intact female cats. METHODS: Cats had renal autograft transplantation without ureteral transection and reimplantation and a contralateral nephrectomy. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured regularly and abdominal ultrasound was performed before surgery, the day after surgery and twice weekly thereafter. Ultrasound-guided renal biopsy was performed on day 7. Cats were euthanatized on day 21. Histology of the autograft, ureter, bladder, vascular anastomoses sites, and contralateral kidney were performed. Observations were compared with those from an historic group of research cats that had extravesicular ureteroneocystostomy and contralateral nephrectomy. RESULTS: Five cats completed the study. Serum creatinine and BUN concentrations increased after surgery, peaking at 3.2+/-0.8 and 77.6+/-15.9 mg/dL, respectively, 1-2 days after surgery. Serum creatinine concentration returned to the reference interval by 6 days after surgery. BUN gradually decreased in all cats but did not return to the reference interval by study end. Serum creatinine and BUN concentrations were consistently lower but not significantly so (P=.29 and .56, respectively) compared with the historic ureteroneocystostomy group. No ultrasonographic abnormalities or renal biopsy histologic abnormalities were observed. At necropsy, 1 autograft had generalized interstitial fibrosis. CONCLUSION: Harvesting the renal graft and the ischemia before revascularization causes impaired renal function after engraftment. CLINICAL RELEVANCE: The process of harvesting and reimplanting the renal graft can contribute to DGF in cats, independent of ureteral obstruction.     

Acute intrinsic renal failure in cats: 32 cases (1997-2004)

OBJECTIVE: To determine patient demographics, clinicopathologic findings, and outcome associated with naturally acquired acute intrinsic renal failure (ARF) in cats. DESIGN: Retrospective case series. ANIMALS: 32 cats with ARF. PROCEDURES: Cats were considered to have ARF if they had acute onset of clinical signs (< 7 days), serum creatinine concentration > 2.5 mg/dL (reference range, 0.8 to 2.3 mg/dL) and BUN > 35 mg/dL (reference range, 15 to 34 mg/dL) in conjunction with urine specific gravity < 1.025 or with anuria or increasing serum creatinine concentration despite fluid therapy and normal hydration status, and no signs of chronic renal disease. Cases were excluded if cats had renal calculi or renal neoplasia. RESULTS: Causes of ARF included nephrotoxins (n = 18 cats), ischemia (4), and other causes (10). Eighteen cats were oliguric. For each unit (mEq/L) increase in initial potassium concentration, there was a 57% decrease in chance of survival. Low serum albumin or bicarbonate concentration at initial diagnosis was a negative prognostic indicator for survival. Initial concentrations of BUN, serum creatinine, and other variables were not prognostic. Seventeen (53%) cats survived, of which 8 cats had resolution of azotemia and 9 cats were discharged from the hospital with persistent azotemia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that survival rates of cats with ARF were similar to survival rates in dogs and that residual renal damage persisted in approximately half of cats surviving the initial hospitalization.     

Effects of benazepril hydrochloride in cats with experimentally induced or spontaneously occurring chronic renal failure

We examined effects of an angiotensin converting-enzyme inhibitor, benazepril hydrochloride (BH), on renal hypertension and chronic renal failure (CRF) in cats. For experimental CRF, healthy cats (n=5) underwent 7/8 renal ablation. After renal insufficiency and hypertension were confirmed by blood urea nitrogen (BUN), serum creatinine, creatinine clearance and telemetric recording of systemic blood pressure, BH was administered orally once daily at 0.9 to 2.0 mg/kg/day for 2 to 3 weeks. Within 2 months after renal ablation, renal failure and hypertension developed as evidenced by significant increases in BUN, serum creatinine and systemic blood pressure (p<0.01 or 0.05) and significantly decreased creatinine clearance accompanied by elevated plasma renin activity, angiotensin I and II, and aldosterone (p<0.01 or 0.05). BH administration corrected systemic hypertension (p<0.05) and significantly reduced angiotensin II and aldosterone (p<0.05). Upon discontinuation of BH, these values returned to the pre-administration levels. Studies on spontaneous CRF enrolled 11 cats with spontaneously occurring CRF. BH was administered orally to 6 cats once daily for 24 weeks at a final dose of 1.0 mg/kg/day, while 5 cats served as control. BH administration reduced serum creatinine and urinary protein concentration in every cat. Results demonstrate that in cats, loss of renal mass leads to activation of the renin-angiotensin-aldosterone system and associated renal hypertension, and indicate that BH is effective in correcting renal hypertension and may provide renal benefits to cats with CRF.     

Evaluation of renal biopsies in cats and dogs — histopathology in comparison with clinical data

Histopathological findings of renal biopsies in cats and dogs with diffuse nephropathies generally lead to an exact diagnosis and facilitate prognostic judgements. Complications following renal biopsy are usually slight, provided the biopsy is performed properly. Routine renal laboratory data have been compared with histopathological findings. High urine protein values are often the result of glomerular lesions, whereas high creatinine values are frequently related to tubulointerstitial lesions. In general, there is no relationship between different types of nephropathy and age; nevertheless animals with chronic tubulointerstitial nephritis were, on average, older than animals with glomerulopathies.     

Characterization of interstitial nephritis in pigs with naturally occurring postweaning multisystemic wasting syndrome

Kidney samples with interstitial nephritis from 26 pigs affected by postweaning multisystemic wasting syndrome (PMWS) were selected. A histologic evaluation was carried out to describe the type of inflammation and its relationship with viral load, as assessed by in situ hybridization (ISH). Of 26 cases, 10 revealed a tubulointerstitial, lymphoplasmacytic nephritis, 11 an interstitial granulomatous nephritis, and 5 both types of inflammation (mixed type). In 4 cases of granulomatous inflammation, the pattern was not classically nodular, and a population of macrophages and lymphocytes was present (interstitial lymphohistiocytic nephritis). ISH confirmed the presence of porcine circovirus type 2 (PCV2) nucleic acid in all cases. The epithelium of the renal tubules was the most constantly ISH-positive structure. In tubulointerstitial nephritis, the higher the number of positive inflammatory cells, the more severe the inflammation. The ISH reaction was more heterogeneous and unpredictable in granulomatous nephritis, with some epithelioid and giant cells positive by ISH. To quantify macrophages distributed in the three patterns of nephritis, immunohistochemical methods using anti-major histocompatibility complex II (anti-MHC-II) and anti-lysozyme antibodies were undertaken, and semiquantitative evaluation was carried out. MHC-II was mainly expressed by lymphocytes in tubulointerstitial nephritis, but did not always stain macrophages in cases of granulomatous (including lymphohistiocytic) nephritis; the anti-lysozyme antibody revealed macrophages when present in tissues. The amount of PCV2 nucleic acid was not apparently associated with the pattern of inflammation (tubulointerstitial or granulomatous). PCV2 load seems to reflect the severity of the lymphoplasmacytic inflammation but not that of granulomatous and lympho histiocytic types.     

Clinical application of plasma clearance of iohexol on feline patients

Glomerular filtration rate (GFR) was estimated by plasma clearance of iohexol (PCio) in 52 conscious cats presented for a variety of reasons to Angel Animal Hospital over a 2-year period. Cats were divided into four groups according to their clinical conditions and reasons for measuring PCio. The median PCio (ml/min/kg) was 3.68 in normal cats (NM), 2.39 in cats with suspected renal disease (SP), 1.35 in cats referred to confirm renal dysfunction (RD), and 0.84 in cats with apparent clinical signs of renal failure (RF). There was a significant difference between the results for each group. The respective medians of blood urea nitrogen (BUN) and plasma creatinine concentration (Pcr) (mg/dl) were 15 and 1.40 in NM cats, 21 and 1.71 in SP cats, 30 and 2.20 in RD cats, and 48 and 3.30 in RF cats. The reference values of BUN and Pcr were 21 +/- 7 mg/dl and 1.5 +/- 0.4 mg/dl (mean +/- SD). Diminished renal function could not be detected in SP cats by either BUN or Pcr, while a marked decrease of GFR was demonstrated before BUN and Pcr increased, indicating the insensitivity of BUN and Pcr in detecting renal dysfunction in cats. PCio can be performed non-invasively in conscious cats, which improves the veterinarian's ability to detect early stages of chronic renal disease.     

Evaluation of blood urea nitrogen and serum creatinine concentrations as indicators of renal dysfunction: a study of 111 cases and a review of related literature.

Blood urea nitrogen concentration (BUN), serum creatinine concentration (SC), and BUN/SC ratios, as recorded for 111 dogs and cats with azotemia, were evaluated to determine their usefulness in evaluation of renal dysfunction. Cases were categorized into prerenal, renal, and post-renal causes of azotemia, on the basis of histologic and clinical criteria. The severity of azotemia varied within groups, but the mean value for degree of azotemia was lowest in the prerenal group. The BUN/SC ratios were highest when azotemia was mild, regardless of cause. The BUN/SC ratios in the 3 groups were not significantly different when the degree of azotemia was considered, indicating that differentiation of renal from extrarenal azotemia was not possible in the dog and cat, on the basis of relative values of BUN and SC. Comparison of BUN/SC ratios in acute and chronic azotemia of comparable magnitude revealed no significant differences between groups, indicating that this ratio cannot be used to differentiate acute and chronic azotemia. Following supportive therapy, BUN decreased significantly (P less than 0.05) more than SC, suggesting that extrarenal factors contributed to the increased BUN and that proportionately more urea than creatinine was excreted by the kidneys during therapy. The BUN/SC ratios varied widely and to a similar degree in all groups examined. Inasmuch as the BUN and SC were not correlated with more accurate measurements of renal function, conclusions could not be drawn concerning the superiority of either factor as a measure of renal function. Many nonrenal factors, previously identified, influence serum concentration of urea and creatinine. In recent studies involving azotemic human beings and rats, it was suggested that up to 25% of the urea and 65% of the creatinine produced in the body is degraded by enteric bacteria rather than excreted directly by the kidneys. These data indicate that neither BUN or SC can be used as precise tests of renal function, although SC is subject to alteration by fewer nonrenal factors than is BUN. In older medical and veterinary medical literature, the use of SC as a prognostic indicator had been advocated. Newer findings on the pathophysiology of creatininemia and retrospective case studies do not support this view. In the present study, severe creatininemia was documented in cases in which primary renal dysfunction did not exist. It was concluded that BUN and SC should continue to be regarded as crude indexes of renal function. Clinical value lies in the relative ease of their determination. Because of their lack of sensitivity, more specific evaluation of renal function (urine concentrating ability, phenolsulfonphthalein excretion) may be indicated when BUN and SC are normal or only slightly elevated. Because extrarenal factors may alter BUN and SC, it is necessary to correlate these values with clinical and other laboratory data to differentiate renal from extra-renal azotemia. Single determinations of BUN or SC provide no basis for prognosis.     

CHANGES IN RENAL FNCTION IN CATS FOLLOWING TREAMENT OF HYPERTHYROIDISM USING131I

Changes in renal fnction of twenty-two cats treated for hyperthyrodism using radioiodine were evaluated. Serum thyroxine (T₄), serum creatinine, blood urea nitrogen (BUN) and urine specificgravity were measured before treatment and 6 and 30 days after treatment. Twenty-two cats had pretreatment and 21 cats had 6 day posttreatment measurement of glomercular filtration rate (GFR) using nuclear medicine imaging techniques. there were significant declines in serum T₄ at 6 days following treatment, but the changes in GFR, serum creatinine and BUN were not significant. At 30 days following treatment, there were significant increases in BUN and serum creatinine and further significant declines in serum T₄. Nine cats were in renal failure prior to treatment and 13 cats were in renal failure 30 days following treatment. Renal failure was defined as BUN greater than 30 mg/dl and/or serum creatinine greater than 1.8 mg/dl with concurrent urine specific gravity less than 1.035. these 13 cats included eight of 9 cats in renal failure prior to treatment on 9 of these 13 cats indicated that all remained in renal failure. Based on receiver operating curve analysis of pretreatment glomerular filtration rate (GFR) in predicting posttreatment renal failure, a value of 2.25 ml/kg/min as a point of maximum sensitivity (100%) and spefificity (78%) was derived, Fifteen of 22 cats had pretratmentGFR measurements of less than 2.25 ml/kg/min. these 15 cats included all 9 cats in renal failure and 65 cats with normal renal clinicopathologic values prior to treatment. at 30 days following treatment, 13 of these 15 cats were in renal failure. The 2 cats not in renal failure had persistently increased serum T₄ values. seven of 22 cats had pretreatment GFR measurements greater than 225 ml/kg/min. None of these 7 cats was in renal failure at 30 days following treatment, all cats having normal BUN, serum creatinine, and urine specific gravity values. It was concluded that significant declines in renal function occur after treatment of hyperthyroidism and this decline is clinically important in cats with renal disease. Pretreatment measurement of GFR is valuable in detecting subclinical renal disease and in predicting which cats may have clinically important declines in renal function following treatment.     

Bilateral renal ischemia as a model of acute kidney injury in cats

The objective of this study was to evaluate the effect of 1h, bilateral, warm ischemia-reperfusion kidney injury as a model of acute kidney injury in the cat. Four adult healthy cats underwent 60 min of bilateral, in vivo renal warm ischemia; three cats were sham operated controls. Kidney function was evaluated with creatinine and BUN concentration, urine protein: creatinine, and glomerular filtration rate. Post-reperfusion endothelin and renin was measured by ELISA and RT-qPCR. Blood pressure (BP), platelet count, and platelet aggregation were monitored. Renal biopsy specimens were evaluated histopathologically. There was significant reduction in renal function characterized by severe azotemia and proximal tubular brush border loss. Changes in renin or endothelin gene expression or serum concentration were not detected. No changes were detected in BP. Platelet count and hematocrit decreased markedly after ischemia and reperfusion. Sixty minutes bilateral renal ischemia is an effective model for acute renal injury.     

N-acetyl-beta-D-glucosaminidase activity in urine of cows with renal parenchymal lesions

OBJECTIVE: To measure N-acetyl-beta-D-glucosaminidase (NAG) activity in urine of cows with renal diseases and to correlate values for NAG activity with renal lesions. ANIMALS: 8 lactating Holstein cows and a Japanese Shorthorn cow, all of which had renal disease. PROCEDURE: Urine samples were collected, and urinary NAG activity and creatinine concentration were measured. The NAG activity was expressed as units per gram of creatinine (NAG index). Cows were euthanatized, necropsy was performed, and correlations between results for urinary NAG index and histopathologic findings for the kidneys were evaluated. RESULTS: The NAG activity and NAG index in urine samples obtained from cows with interstitial nephritis were high, ranging from 4.2 to 13.6 U/L and 3.5 to 23.0 U/g, respectively. A cow with renal amyloidosis also had high values for urinary NAG activity and NAG index. Histologic examination of the kidneys revealed various kinds of parenchymal lesions. However, urinary NAG index in cows with enzootic bovine leukosis was low. CONCLUSIONS AND CLINICAL RELEVANCE: Cows with renal diseases had high urinary NAG indexes that correlated well with their renal lesions, except for cows with enzootic bovine leukosis. Therefore, measurement of NAG index in urine samples has the potential to provide new perspectives on clinical diagnosis of renal disease in cattle.     

Scintigraphic, sonographic, and histologic evaluation of renal autotransplantation in cats.

OBJECTIVE: To determine scintigraphic, sonographic, and histologic changes associated with renal autotransplantation in cats. ANIMALS: 7 adult specific-pathogen-free cats: 5 males, 2 females, 1 to 9 years old. PROCEDURE: Renal autotransplantation was performed by moving a kidney (5 left, 2 right) to the left iliac fossa. Before and at multiple times after surgery, for a total of 28 days, cats were evaluated by B-mode and Doppler ultrasonography, scintigraphy, and renal biopsy. RESULTS: By 24 hours after surgery, a significant decrease (42%) in mean glomerular filtration rate (GFR) and an increase in mean renal size (81% increase in cross-sectional area) were evident in the transplanted kidney, compared with preoperative values. By postsurgery day 28, reduction in GFR was 23%. Significant changes in renal blood flow velocity were identified in both kidneys. Consistent changes in resistive index or pulsatility index for either kidney could not be identified. When all postoperative histologic data were combined, the histologic score, indicating degree and numbers of abnormalities detected, for the transplanted kidney was significantly higher than that for the control kidney. CONCLUSIONS: Significant changes in renal function, size, and histologic abnormalities develop secondary to acute tubular necrosis in cats after uncomplicated renal autotransplantation. CLINICAL RELEVANCE: Evaluation of renal size and function may be of benefit for clinical evaluation of feline renal transplant patients, whereas measurement of the resistive index may be of little clinical value.     

Evaluation of the Clinical and Histologic Features of Renal Allograft Rejection in Cats

OBJECTIVES: To describe the clinical signs and histopathologic features of renal allograft rejection in cats, and to provide a historical, untreated control group for use in future studies of feline renal allograft rejection. ANIMALS: Fourteen adult research cats. METHODS: Renal transplantation and bilateral nephrectomy were performed in pairs of immunogenically mismatched cats. A physical examination was performed, and packed cell volume, total protein, and plasma creatinine concentrations were measured each day after surgery. The cats were euthanatized when plasma creatinine concentration exceeded 7 mg/dL or when weight loss exceeded 20%. Renal histopathology was scored according to the Banff 97 criteria by 3 pathologists. RESULTS: Nine cats completed the study. Plasma creatinine exceeded 7 mg/dL in 5 cats, weight loss exceeded 20% in 3 cats, and 1 cat was found dead. Clinical signs in cats with rejection were nonspecific or absent. Rectal temperature decreased by 0.8 +/- 0.5 degrees C in the 24 hours before euthanasia. The pathologists agreed on the allograft histopathologic category in 6 of 9 cats. The histologic consensus was acute/active rejection in 8 cats and normal in 1 cat. Median survival time of the 8 cats with histologically confirmed allograft rejection was 23 days (range, 8-34 days). CONCLUSIONS AND CLINICAL RELEVANCE: Renal allograft rejection is associated with minimal clinical signs. Therefore, plasma creatinine concentration should be measured routinely in patients with a functioning allograft. An increase in plasma creatinine concentration is highly suspicious for allograft rejection, although a biopsy of the renal allograft is needed for definitive diagnosis.     

Interstitial nephritis in cats inoculated with Crandell Rees feline kidney cell lysates

Parenteral administration of Crandell Rees feline kidney (CRFK) cell lysates or feline herpesvirus 1, calicivirus, and panleukopenia virus-containing vaccines (FVRCP) grown on CRFK cells induces antibodies against CRFK cells. These antibodies also react with feline renal cell extracts. The purpose of this study was to determine whether interstitial nephritis would be detected in cats that were immunologically sensitized with CRFK lysates, boosted with CRFK lysates, and then biopsied 2 weeks after the booster. Cats (2 per group) were immunologically sensitized against CRFK lysates by administering 10 microg, 50 microg, or 50 microg plus alum 13 times (12 times in the first 50 weeks) over 2 years. Two cats were inoculated three times, 4 weeks apart with an FVRCP vaccine for intranasal administration as kittens, boosted 50 and 102 weeks later, and then renal biopsies taken 2 weeks after the last booster. Neither of the cats vaccinated with the FVRCP for intranasal administration had detectable renal inflammation. One cat in each of the three CRFK lysate sensitization groups had lymphocytic-plasmacytic interstitial nephritis.     

Renal pathology in specific-pathogen-free chickens inoculated with a waterfowl-origin type A influenza virus

Five-week-old specific-pathogen-free chickens inoculated intravenously with a waterfowl-origin type A influenza virus (A/mallard/Ohio/184/86) had swollen and mottled kidneys on days 3, 5, and 7 postinoculation (PI) and multiple raised nodules on days 5, 10, and 20 PI. Histologically, the kidneys had multifocal heterophilic tubulointerstitial nephritis with epithelial necrosis on day 3 PI, lymphoplasmacytic tubulointerstitial nephritis on day 5 PI, and fibrosing interstitial nephritis with cortical lobular collapse, atrophic tubules, glomerular aggregates, and interstitial lymphoid follicles and aggregates on days 7, 10, and 20 PI. Heterophilic intratubular medullary-cone nephritis was present in dead or moribund chickens on days 3 and 5 PI. Furthermore, the presence of mild multifocal heterophilic tubulointerstitial nephritis on day 20 PI suggests that a waterfowl-origin strain of type A influenza virus of low pathogenicity has the potential to produce acute and chronic active nephritis in the chicken and that the kidney is a potential site for influenza viral persistence. The acute, subacute, and chronic histopathologic renal lesions of this influenza virus in chickens are similar to lesions reported for some nephropathogenic infectious bronchitis viruses and avian nephritis picornavirus.     

Urinary excretion of N-acetyl-beta-D-glucosaminidase and its isoenzymes in cats with urinary disease

The present study was designed to assess the clinical usefulness of measurement of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and its isoenzymes in cats with urinary disease. Thirty-five healthy cats and 9 cats with renal disease were used. Furthermore, a 5-year-old female cat was administered a large amount of sulfonamide in order to induce acute renal failure, and urine samples were collected for the assay of NAG activity and its isoenzymes. Urinary NAG activity was measured using p-nitrophenyl N-acetyl-beta-D-glucosaminide, and expressed as units per gram of urinary creatinine (NAG index). Urinary NAG isoenzymes were assayed by use of the mini-column method and electrophoresis. The overall mean value of urinary NAG index in healthy cats was 1.6+/-1.5 U/g. Urinary NAG index varied from 6.2 to 35.5 U/g in cats with chronic renal failure. There was no significant correlation between BUN, serum creatinine concentration and urinary NAG index. In cats with feline lower urinary tract disease, normal values of urinary NAG index were observed. In the urine samples of healthy cats, the proportions of NAG isoenzyme A (NAG-A) and isoenzyme B (NAG-B) were 79.1+/-4.4% and 21.0+/-4.4%, respectively, as assayed by the mini-column method. In the assay of NAG isoenzymes by electrophoresis, the proportions of NAG-A and NAG-B in healthy cats were 66.6+/-5.8% and 33.4+/-5.8%, respectively. The proportion of NAG-B as measured by electrophoresis was significantly larger (p<0.05) than that obtained with the mini column method. A feline case of acute renal failure experimentally-induced by sulfonamide showed elevation of urinary NAG index, NAG-A and NAG-B after injection of sulfonamide. The increase in NAG-B was larger than that of NAG-A. From the results reported here, measurement of urinary NAG and its isoenzymes seems to yield information about tubular damage at an early stage in cats with urinary disease.     

Applications and Outcome of Hemodialysis in Cats: A Review of 29 Cases

Hemodialysis (HO) has been used in the management of renal failure in dogs, but its feasibility has not been reported for uremic cats. Therefore, we investigated the technical possibility, efficacy, and complications of intermittent HD in cats with severe uremia. A total of 160 HD treatments were performed on 29 cats with acute renal failure (ARF) (n = 15), chronic renal failure (CRF) (n = 6), or acute on CRF (n =8) between November 1993 and June 1996. Hemodialysis treatments were performed with transcutaneous dialysis catheters using a bicarbonate-based delivery system, sodium modeling, and volumetric-controlled ultrafiltration. Presenting serum chemistries (mean ± SD) for all cats were creatinine, 16.4 ± 7.5 mg/dL; blood urea nitrogen (BUN), 229 ± 87 mg/dL; phosphate, 15.4 ± 5.4 mg/dL; potassium, 6.0 ±1.6 mEq/L; and HCO^-₃, 16.0 ± 4.4 mEq/L. For intensive HD treatments, pre-HD versus post-HD creatinine changed from 10.3 ± 4.4 to 1.6 ± 0.9 mg/dL and BUN from 105 ± 33 to 8 ±10 mg/dL. One or more adverse events occurred during 111 (69%) treatments. Dialysis-related events included hypotension, dialysis dysequilibrium, clotting, and bleeding. Nine of 15 (60%) cats with ARF and 1 cat with CRF recovered sufficiently to survive without ongoing need for HD. For the remaining cats, the proximate causes of death were dialysis related in 9 cats, uremia related in 6 cats, and iatrogenic or unknown in 4 cats. Hemodialysis is technically feasible and effectively controls the biochemical disturbances of uremic cats. It is especially valuable for the management of severe ARF, permitting recovery in a large number of cats refractory to conventional therapy. Technical complications and chronic debility, however, may limit its usefulness for cats with advanced CRF.     

Prognostic factors in cats with chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) is a common cause of morbidity and mortality in cats. HYPOTHESIS: Some baseline variables are associated with shorter survival times in cats with CKD. ANIMALS: Client-owned cats. METHODS: Cats with CKD with initial plasma creatinine concentration > or =2.0 mg/dL and urine specific gravity (USG) < or = 1.025 were recruited into a prospective clinical trial that compared benazepril with a placebo. We describe baseline variables in 190 cats and their influence on renal survival time in the placebo group (95 cats), which was followed for up to 1,097 days. Renal survival time was defined as the time from initiation of therapy to the need for parenteral fluid therapy, euthanasia, or death related to renal failure. RESULTS: Of the 95 cats treated with a placebo, 58 were censored and 37 reached the renal survival end point (died, n = 0; euthanized, n = 17; parenteral fluids, n = 12; parenteral fluids followed by euthanasia, n = 8). Increased plasma creatinine concentration, increased urine protein-to-creatinine ratio (UPC), and increased blood leukocyte count were significantly (P < .01) associated with a shorter renal survival time and were independent risk factors. Increased concentrations of plasma phosphate or urea, and lower blood hemoglobin concentration or hematocrit were significantly (P < .01) associated with a shorter renal survival time and were dependent risk factors, because they also were significantly (P < .01) correlated with plasma creatinine concentration at baseline. CLINICAL IMPORTANCE: Several variables were significantly associated with a shorter renal survival time in cats with CKD.     

Proteomic analysis of urine from male dogs during early stages of tubulointerstitial injury in a canine model of progressive glomerular disease

Background: Sensitive and specific noninvasive biomarkers for tubulointerstitial injury are lacking, and proteomic techniques provide a powerful tool for biomarker discovery. Objective: The aim of this study was to identify novel urinary biomarkers of early tubulointerstitial injury in canine progressive renal disease using both 2‐dimensional differential in‐gel electrophoresis (2‐D DIGE), which identifies individual proteins, and surface‐enhanced laser desorption ionization time‐of‐flight mass spectrometry (SELDI‐TOF), which generates protein peak profiles. Methods: Urine was collected from 6 male dogs with X‐linked hereditary nephropathy (XLHN) at 2 time points (TP): 1) the onset of overt proteinuria (urine protein:creatinine ratio>2) and 2) the onset of azotemia (creatinine ≥1.2 mg/dL); corresponding renal biopsies were analyzed from 3 of the dogs. Urine samples from the 6 dogs were subjected to analysis by 2‐D DIGE and SELDI‐TOF. Urinary retinol‐binding protein (RBP) was evaluated in 25 male dogs with XLHN and normal control dogs by Western blot analysis. Results: Clinical data and histologic evaluation revealed reduced renal function and increased tubulointerstitial fibrosis at TP 2. A number of urine proteins and protein peaks were differentially present at the 2 time points, with several known biomarkers of renal disease identified in addition to several promising new biomarkers. RBP was first detected in urine approximately 2 months before onset of azotemia (TP 2), but after onset of overt proteinuria, and amounts increased with progression of disease. Conclusions: Proteomic techniques were successfully used to identify urinary biomarkers of renal disease in dogs with XLHN. Urinary RBP is a promising biomarker for early detection of tubulointerstitial damage and progression to end‐stage renal disease.