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Hemoglobin (Hb) constitutes an important protein in clinical diagnostics-both in humans and animals. Among the high number of sequence variants, some can cause severe diseases. Moreover, chemical modifications such as glycation and carbamylation serve as important biomarkers for conditions such as diabetes and kidney diseases. In clinical routine analysis of glycated Hb, sequence variants or other Hb proteoforms can cause interference, resulting in wrong quantification results. We present a versatile and flexible capillary zone electrophoresis-mass spectrometry screening method for Hb proteoforms including sequence variants and modified species extracted from dried blood spot (DBS) samples with virtually no sample preparation. High separation power was achieved by application of a 5-layers successive multiple ionic polymer layers-coated capillary, enabling separation of positional isomers of glycated α- and β-chains on the intact level. Quantification of glycated Hb was in good correlation with the results obtained in a clinical routine method. Identification and characterization of known and unknown proteoforms was performed by fragmentation of intact precursor ions. N-Terminal and lysine glycation could be identified on the α- and β-chain, respectively. The versatility of the method was demonstrated by application to dog and cat DBS samples. We discovered a putative new sequence variant of the β-chain in dog (T38 → A). The presented method enables separation, characterization, and quantification of intact proteoforms, including positional isomers of glycated species in a single run. Combined with the simple sample preparation, our method represents a valuable tool to be used for deeper characterization of clinical and veterinary samples.

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin–stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex–mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases—that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed.

Early identification of patients with chronic kidney disease is considered important for implementing therapeutic interventions aimed at slowing further progression of the disease. This chapter describes the diagnostic techniques including historical findings, the clinical examination, laboratory diagnosis and imaging. Measurement of glomerular filtration rate is discussed in detail.

Renal function can be monitored by estimation of the glomerular filtration rate (GFR), for example, through measurement of the plasma clearance of a marker that is freely filtrated through the kidney without reabsorption. It has been proposed that iohexol is the most accurate marker for GFR determination in cats and dogs. However, there is a need for a validated capillary electrophoretic method that covers the concentration range for a full curve clearance estimate of iohexol. In the final method, the plasma samples were protein precipitated and the supernatant was analyzed in a background electrolyte containing borate buffer (0.06 m, pH 10.0). The method developed was proved to be linear (concentration range 18- 2900 mg/L) and had a good precision (e.g. 2.3-2.9% at 88 mg/L) and accuracy (e.g. 101-105% at 88 mg/L). Finally, the method was compared with a previously published and validated HPLC-UV method by parallel analysis of clinical plasma samples from dogs and cats administered Omnipaque®. This comparison showed excellent agreement between the two methods and no proportional or systematic error was observed. The proposed method is simple and has a low cost per sample, which makes it applicable for routine analysis.

Polynomial equations for one-compartment correction of slope-intercept glomerular filtration rate (GFR) will underestimate values at high clearance rates. Non-polynomial correction equations that are independent of patient size and renal function would be advantageous and may have cross-species use.The study explored the theoretical basis of firstly the Jodal and Brochner-Mortensen one-compartment correction equation, replacing plasma volume with extracellular fluid volume, and secondly an equation described by Peters. One-compartment correction factors (a which is related to plasma volume and v which is related to extracellular fluid volume) which avoided the need for scaling to body size were developed. Both factors were determined from the biexponential clearance curve of the markers iohexol and (51)Cr-EDTA in humans and iohexol in cats and dogs. Relationships between a and v and filtration function and body size were then determined using data from humans, cats and dogs to assess their validity and compare this with theoretical predictions.In all species, v was higher than a, as theoretically predicted. Both were significantly higher in humans than cats and dogs, ruling out cross-species use. Significant relationships were present between v and measures of filtration function in humans, but were weak with respect to a. Neither a nor v showed significant relationships with filtration function in animals or with body size in any species.a and v (which are factors independent of body size) can be used interchangeably for correcting slope-intercept clearance. However values of both for humans are higher compared to cats and dogs. Therefore a single cross-species factor cannot be used.

The purpose of this report was to provide consensus recommendations for the use of immunosuppressive therapy in dogs with active glomerular diseases. Recommendations were developed based on comprehensive review of relevant literature on immunosuppressive therapy of glomerular disease in dogs and humans, contemporary expert opinion, and anecdotal experience in dogs with glomerular disease treated with immunosuppression. Recommendations were subsequently validated by a formal consensus methodology. The Study Group recommends empirical application of immunosuppressive therapy for dogs with severe, persistent, or progressive glomerular disease in which there is evidence of an active immune-mediated pathogenesis on kidney biopsy and no identified contraindication to immunosuppressive therapy. The most compelling evidence supporting active immune-mediated mechanisms includes electron-dense deposits identified with transmission electron microscopic examination and unequivocal immunofluorescent staining in the glomeruli. For diseases associated with profound proteinuria, attendant hypoalbuminemia, nephrotic syndrome, or rapidly progressive azotemia, single drug or combination therapy consisting of rapidly acting immunosuppressive drugs is recommended. The Study Group recommends mycophenolate alone or in combination with prednisolone. To minimize the adverse effects, glucocorticoids should not be used as a sole treatment, and when used concurrently with mycophenolate, glucocorticoids should be tapered as quickly as possible. For stable or slowly progressive glomerular diseases, the Study Group recommends mycophenolate or chlorambucil alone or in combination with azathioprine on alternating days. Therapeutic effectiveness should be assessed serially by changes in proteinuria, renal function, and serum albumin concentration. In the absence of overt adverse effects, at least 8 weeks of the rapidly acting nonsteroidal drug therapy and 8-12 weeks of slowly acting drug therapy should be provided before altering or abandoning an immunosuppressive trial.

Background Validated methods of estimating glomerular filtration rate (GFR) in cats requiring only a limited number of samples are desirable. Hypothesis/Objectives To test a single sample method of determining GFR in cats. Animals The validation population (group 1) consisted of 89 client-owned cats (73 nonazotemic and 16 azotemic). A separate population of 18 healthy nonazotemic cats (group 2) was used to test the methods. Methods Glomerular filtration rate was determined in group 1 using corrected slope-intercept iohexol clearance. Single sample clearance was determined using the Jacobsson and modified Jacobsson methods and validated against slope-intercept clearance. Extracellular fluid volume (ECFV) was determined from slope-intercept clearance with correction for the 1 compartment assumption and by deriving a prediction formula for ECFV (ECFVPredicted) based on the body weight. The optimal single sample method was tested in group 2. Results A blood sample at 180 minutes and ECFVPredicted were optimal for single sample clearance. Mean ± SD GFR in group 1 determined using the Jacobsson and modified Jacobsson formulae was 1.78 ± 0.70 and 1.65 ± 0.60 mL/min/kg, respectively. When tested in group 2, the Jacobsson method overestimated multisample clearance. The modified Jacobsson method (mean ± SD 2.22 ± 0.34 mL/min/kg) was in agreement with multisample clearance (mean ± SD 2.19 ± 0.34 mL/min/kg). Conclusions and Clinical Importance The modified Jacobsson method provides accurate estimation of iohexol clearance in cats, from a single sample collected at 180 minutes postinjection and using a formula based on the body weight to predict ECFV. Further validation of the formula in patients with very high or very low GFR is required.

A sensitive and specific high performance liquid chromatography-ultraviolet detection (HPLC-UV) method for quantitative determination of exo- and endo-iohexol in cat and dog serum/plasma is presented. Sample preparation consisted of a protein precipitation step performed by adding 15 μL of trifluoroacetic acid to 100 μL of serum/plasma. Following vortexing and centrifugation, an aliquot of the supernatant was injected onto a polymeric PLRP-S column (250 mm × 4.6 mm i.d., dp: 8 μm, 100 Å), maintained at 30 °C. The mobile phase consisted of water (A) and methanol (B) and a gradient elution (flow-rate: 1.0 mL min(-1), total run-time: 21 min). The UV detector was set at a wavelength of 254 nm. Matrix-matched calibration graphs were prepared for both exo- (0.44-657 μg mL(-1)) and endo-iohexol (0.62-93.0 μg mL(-1)). Correlation and goodness-of-fit coefficients were between 0.9985-0.9999 and 4.44-9.87%, respectively. Limits of quantification and detection were 0.44 and 0.15 μg mL(-1) for exo-iohexol and 0.62 and 0.20 μg mL(-1) for endo-iohexol, respectively. Results for within-day and between-day precision and accuracy fell within the ranges specified. The reported method is simple and cost-effective. It has been successfully used for the analysis of exo- and endo-iohexol in serum/plasma samples of cats and dogs as part of pharmacokinetic studies with iohexol in order to determine plasma clearance of exo- and endo-iohexol. This indicates the usefulness of the developed method for application in the field of veterinary clinical practice and research.

Objective—To develop a formula for correcting slope-intercept plasma iohexol clearance in cats and to compare clearance of total iohexol (TIox), endo-iohexol (EnIox), and exo-iohexol (ExIox). Animals—20 client-owned, healthy adult and geriatric cats. Procedures—Plasma clearance of TIox was determined via multisample and slope-intercept methods. A multisample method was used to determine clearance for EnIox and ExIox. A second-order polynomial correction factor was derived by performing regression analysis of the multisample data with the slope-intercept data and forcing the regression line though the origin. Clearance corrected by use of the derived formula was compared with clearance corrected by use of Brochner-Mortensen human and Heiene canine formulae. Statistical testing was applied, and Bland-Altman plots were created to assess the degree of agreement between TIox, EnIox, and ExIox clearance. Results—Mean ± SD iohexol clearance estimated via multisample and corrected slope-intercept methods was 2.16 ± 0.35 mL/min/kg and 2.14 ± 0.34 mL/min/kg, respectively. The derived feline correction formula was Clcorrected = (1.036 × Cluncorrected) – (0.062 × Cluncorrected2), in which Cl represents clearance. Results obtained by use of the 2 methods were in excellent agreement. Clearance corrected by use of the Heiene formula had a linear relationship with clearance corrected by use of the feline formula; however, the relationship of the feline formula with the Brochner-Mortensen formula was nonlinear. Agreement between TIox, EnIox, and ExIox clearance was excellent. Conclusions and Clinical Relevance—The derived feline correction formula applied to slope-intercept plasma iohexol clearance accurately predicted multisample clearance in cats. Use of this technique offers an important advantage by reducing stress to cats associated with repeated blood sample collection and decreasing the costs of analysis.

Background: Proteinuria is a feature of pyometra-associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. Objectives: To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers. Animals: Forty-seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. Methods: Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C-reactive protein, urinary thromboxane B2) and tubular function (urinary retinol-binding protein, urinary N-acetyl-β-d-glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 2+ or 3+ were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs. Results: UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05–8.69) compared with healthy bitches (0.08, 0.02–0.16) (P 0.5, 12 had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile. Conclusion: Dogs with pyometra and UPC>1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra-associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis in dogs.

NSAIDs and cats Non-steroidal anti-inflammatory drugs (NSAIDs) are an important class of drug in feline medicine, having analgesic, anti-inflammatory and antipyretic activity. While most published data on their use in this species relate to short-term (often perioperative) therapy, there is increasing evidence of the value of these drugs in treating chronic pain in cats (for example, that associated with degenerative joint disease), and some NSAIDs have now become licensed for long-term use in cats in some geographies. Most of our knowledge of therapeutic mechanisms or adverse drug reactions associated with NSAIDs is extrapolated from work in other species, and there is a paucity of published data relating to cats. Guidelines These guidelines have been drawn together by an expert panel, which have reviewed the current literature on long-term NSAID use in cats and other species, and developed guidance on their use based on this information. The aim is to provide practical information for veterinarians to encourage appropriate NSAID therapy whenever cats will benefit from the use of these drugs.

Objective—To compare 2 methods for estimation of glomerular filtration rate (GFR), study the effects of age and body size on GFR estimates, and provide a reference range for estimated GFR in clinically normal cats. Animals—57 cats. Procedures—In each cat, GFR was estimated via plasma clearance of iohexol and creatinine. Results of a 1-compartmental model (CL1comp) were calibrated to a trapezoidal method estimate (CLtrap) by use of a correction formula applicable to dogs or humans and standardized to body weight; for iohexol clearance, data were also standardized to extracellular fluid volume (ECFV). For all 57 cats, method comparison was performed via agreement analysis. Reference ranges for GFR derived by the different methods were established by use of data from a subset of 51 cats after exclusion of 6 cats that were azotemic, Birman, or both. Results—In 57 cats, mean CLtrap of creatinine was 0.29 mL/min/kg (13%) higher than CLtrap of iohexol. In 51 nonazotemic cats, mean CLtrap was 2.26 mL/min/kg for iohexol (reference range, 1.02 to 3.50 mL/min/kg) and 2.55 mL/min/kg for creatinine (reference range, 1.27 to 3.83 mL/min/kg). Values of GFR/kg or GFR standardized to liters of ECFV did not decrease with increasing age. A negative linear relationship was detected between body weight and estimated GFR/kg or GFR standardized to liters of ECFV. Conclusions and Clinical Relevance—Reference ranges for estimated GFR via plasma clearance of iohexol and creatinine should facilitate early detection of impaired renal function in cats, although body weight should be taken into account.

Background: Glomerular filtration rate (GFR) decreases in the aging human kidney, but limited data exist in dogs. Hypothesis: There is an effect of age and body size on estimated GFR in healthy dogs. Animals: One hundred and eighteen healthy dogs of various breeds, ages, and body weights presenting to 3 referral centers. Methods: GFR was estimated in clinically healthy dogs between 1 and 14 years of age. GFR was estimated from the plasma clearance of iohexol, by a compartmental model and an empirical correction formula, normalized to body weight in kilograms or liters of extracellular fluid volume (ECFV). For data analysis, dogs were divided into body weight quartiles 1.8–12.4, 13.2–25.5, 25.7–31.6, and 32.0–70.3 kg. Results: In the complete data set, there was no trend toward lower estimated GFR/kg or GFR/ECFV with increasing age. GFR decreased with age in dogs in the smallest weight quartile only. A significant negative linear relationship was detected between body weight and estimated GFR/kg and GFR/ECFV. Reference ranges in different weight quartiles were 1.54–4.25, 1.29–3.50, 0.95–3.36, and 1.12–3.39 mL/min/kg, respectively. Standardization to ECFV rather than kilogram body weight did not produce substantial changes in the relationships between GFR estimates and age or weight. Conclusions and Clinical Importance: Interpretation of GFR results for early diagnosis of renal failure should take into account the weight and the age of the patient for small dogs.

Animal studied A tumor of the left eye with involvement of the brain and kidney was diagnosed in a 4-year-old Neapolitan mastiff. Procedure The dog presented with acute glaucoma of the left eye. Peripheral corneal vascularization and severe corneal edema obscured examination of deeper structures. Because of concurrent progressive neurologic signs the dog was euthanized and a postmortem examination was performed. The eyes, brain and samples from the lung, heart, liver and kidneys were fixed in 4% neutral buffered formalin and embedded in paraffin wax. Sections were examined by light microscopy including histochemical and immunohistochemical staining. Results The ocular tumor originated from the ciliary body and was composed of small islets and cords of poorly differentiated, oval to polyhedral cells surrounded by abundant ground substance. Areas with chondroid differentiation were observed. Rosettes were not found. Metastases with the same morphology were present in the brain and in one kidney. Conclusion An intraocular malignant teratoid medulloepithelioma with metastases to the brain and kidney is presented.

Objective—To determine vasopressin (VP) secretory capacity during osmotic stimulation and the response to desmopressin treatment in dogs with pyometra and control dogs. Animals—6 dogs with pyometra before and after ovariohysterectomy and 6 control dogs. Procedure—Urine osmolality (Uosm) was measured during 12 hours. Values measured on the first day defined the basal Uosm pattern. On the second day, dogs were given desmopressin to induce a desmopressin-stimulated Uosm pattern. On day 3, the VP response to osmotic stimulation was examined. Results—Median Uosm on day 1 was 340 mOsm/kg (range, 104 to 1,273 mOsm/kg) and 807 mOsm/kg (range, 362 to 1,688 mOsm/kg) in dogs with pyometra before and after surgery, respectively, and 1,511 mOsm/kg (range, 830 to 1,674 mOsm/kg) in control dogs. Median Uosm during desmopressin treatment was 431 mOsm/kg (range, 168 to 1,491 mOsm/kg) and 1,051 mOsm/kg (range, 489 to 1,051 mOsm/kg) in dogs with pyometra before and after surgery, respectively, and 1,563 mOsm/kg (range, 1,390 to 2,351) in control dogs. In dogs with pyometra, threshold for VP secretion was lower before surgery (median, 340 mOsm/kg; range, 331 to 366 mOsm/kg) than after surgery (median, 358 mOsm/kg; range, 343 to 439 mOsm/kg) or in control dogs (median, 347 mOsm/kg; range, 334 to 360 mOsm/kg). Highest maximum plasma VP values were found in dogs with pyometra. Conclusions and Clinical Relevance—Dogs with pyometra had increased urine concentration in response to desmopressin but not to the degree of control dogs, whereas VP secretory ability was not reduced. (Am J Vet Res 2004;65:404–408)

Renal function can be monitored by estimation of the glomerular filtration rate (GFR), for example, through measurement of the plasma clearance of a marker that is freely filtrated through the kidney without reabsorption. It has been proposed that iohexol is the most accurate marker for GFR determination in cats and dogs. However, there is a need for a validated capillary electrophoretic method that covers the concentration range for a full curve clearance estimate of iohexol. In the final method, the plasma samples were protein precipitated and the supernatant was analyzed in a background electrolyte containing borate buffer (0.06 m, pH 10.0). The method developed was proved to be linear (concentration range 18- 2900 mg/L) and had a good precision (e.g. 2.3-2.9% at 88 mg/L) and accuracy (e.g. 101-105% at 88 mg/L). Finally, the method was compared with a previously published and validated HPLC-UV method by parallel analysis of clinical plasma samples from dogs and cats administered Omnipaque®. This comparison showed excellent agreement between the two methods and no proportional or systematic error was observed. The proposed method is simple and has a low cost per sample, which makes it applicable for routine analysis.

The urinary enzyme markers of renal damage, alkaline phosphatase (AP), gamma-glutamyl transferase (GGT) and N-acetyl-beta-glucosaminidase (NAG), glomerular filtration rate (GFR) and renal biopsies were studied to evaluate renal status in dogs with pyometra. After ovariohysterectomy, urinary enzymes were measured daily for 12 days in 55 dogs, and again at a later follow-up visit. Thirteen dogs had high levels of at least one enzyme at initial presentation. Seventeen dogs had a transient increase in urinary enzyme values between one and five days after surgery. Enzyme values usually declined to low activities within 12 post-operative days. Renal biopsies demonstrated tubular abnormalities in many dogs. Mean GFR was 2.4 and 2.0 ml min(-1) kg(-1), respectively on day 1 post-operatively and at the follow-up visit 1-4 months later. High urinary enzyme values often reflected extensive lesions in renal proximal tubular cells and sometimes reduced GFR.

Objective—To compare pharmacokinetics and clearances of creatinine and iohexol as estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function. Animals—50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function. Procedures—Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA. Results—Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods. Conclusions and Clinical Relevance—Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range.

Objective—To compare plasma clearance of inulin and iohexol determined by use of 9 plasma samples for evaluation of glomerular filtration rate in dogs and to evaluate limited-sample approaches for evaluation of plasma clearance of these markers. Animals—43 dogs of various breeds that weighed between 5.5 and 63 kg and that had various degrees of renal function. Procedures—9 plasma samples were obtained from each dog at 5 minutes to 6 hours after IV bolus injection of iohexol and inulin. Clearance was calculated by use of results for all 9 samples (ie, reference method). Results for 3 limited-sample strategies for determination of plasma clearance of iohexol and inulin were compared with results for the reference method. Results—Mean clearance of inulin and iohexol for the reference method was 2.72 and 2.48 mL/min/kg, respectively. The mean difference between clearance of these 2 markers for the reference method was 0.24 mL/min/kg. In general, use of the limited-sample strategies yielded clearance values similar to those for the reference method. More accurate estimates of clearance were obtained for iohexol than for inulin by use of the limited-sample methods. Conclusions and Clinical Relevance—Use of iohexol and inulin yielded similar but not identical results for plasma clearance. Accuracy for limited-sample methods would be acceptable for many clinical and research situations. (Am J Vet Res 2010;71:1100–1107)

Two unrelated Ragdoll cat mothers in Norway were found dead from renal disease. The histopathology was consistent with oxalate nephrosis with chronic or acute-on-chronic underlying kidney disease. Both cats had offspring and relatives with signs of urinary tract disease, including a kitten dead with urethral gravel. Eleven living Ragdoll cats, including nine relatives of the dead cats and the male father of a litter with similarly affected animals, were tested for primary hyperoxaluria (PH) type 1 and 2 by urine oxalate and liver enzyme analysis. Renal ultrasound revealed abnormalities in five living cats. One of these was azotaemic at the time of examination and developed terminal kidney disease 9 months later. A diagnosis of PH was excluded in 11 cats tested. The inheritance and aetiological background of the renal disease present in the breed remains unresolved at this point in time.

Background Age-related changes in renal histomorphology are described, while the presence of glomerulonephritis in dogs with pyometra is controversial in current literature. Methods Dogs with pyometra were examined retrospectively for evidence of secondary renal damage and persisting renal disease through two retrospective studies. In Study 1, light microscopic lesions of renal tissue were graded and compared in nineteen dogs with pyometra and thirteen age-matched control bitches. In Study 2, forty-one owners of dogs with pyometra were interviewed approximately 8 years after surgery for evidence ofclinical signs of renal failure in order to document causes of death/euthanasia. Results Interstitial inflammation and tubular atrophy were more pronounced in dogs with pyometra than in the control animals. Glomerular lesions classified as glomerular sclerosis were present in both groups. No unequivocal light microscopic features of glomerulonephritis were observed in bitches in any of the groups. Two bitches severely proteinuric at the time of surgery had developed end stage renal disease within 3 years. In five of the bitches polyuria persisted after surgery. Most bitches did not show signs of kidney disease at the time of death/euthanasia. Conclusion Tubulointerstitial inflammation was observed, but glomerular damage beyond age-related changes could not be demonstrated by light microscopy in the dogs with pyometra. However, severe proteinuria after surgery may predispose to development of renal failure.

Objective—To evaluate quantification of the amount of carbamylated hemoglobin (CarbHb), using capillary electrophoresis (CE) and a new dynamic capillary coating system to separate hemoglobin derivatives, and to assess the use of CarbHb amounts to evaluate long-term urea exposure and differential diagnoses of azotemia in dogs. Animals—8 dogs with renal failure, 2 dogs with diabetes mellitus, and 7 control dogs. Procedure—Optimal analytic conditions for separation of CarbHb and other hemoglobin derivatives in blood samples obtained from dogs were determined, using a commercial analysis system developed for the detection of glycohemoglobin Hb A1c (GlycHb) in human blood samples. Relative content of hemoglobin derivatives in blood from 10 dogs with renal failure or endocrine diseases were compared with values for 7 dogs without renal or endocrine diseases. Results—Satisfactory resolution of hemoglobin derivatives was obtained, which permitted identification and quantitation of the amount of CarbHb as a percentage of the total amount of hemoglobin. Normal or increased amounts of GlycHb did not interfere with CarbHb analysis. Dogs with chronic renal failure had considerably higher peak amounts of CarbHb than dogs with acute renal failure, a dog with chronic renal failure that was treated by use of hemodialysis, or dogs without renal disease. Conclusions and Clinical Relevance—Amounts of CarbHb in blood samples obtained from dogs can be readily quantified by use of capillary electrophoresis. Assessment of the amount of CarbHb can be used to facilitate evaluation of the cause of azotemia in dogs. (Am J Vet Res 2001;62:1302–1306)

The purpose of the present study was to compare different pharmacokinetic models for estimation of glomerular filtration rate (GFR) in 50 dogs with pyometra. GFR was estimated by plasma clearance (CLplasma) of iohexol by four 1-compartment methods (CL1c), a 2-compartment method (CL2c), and the trapezoidal method (CLtr). Regression analysis was performed to establish correction formulas for prediction of CLtr from the CL1c values and to find optimal times of sampling. Standardization of clearance values to body weight (kg), body surface area (m2) and extracellular fluid volume (ECFV) was compared by ranking of values. CLtr and CL2c values were similar, whereas CL1c overestimated CLtr. CLtr could be predicted from 2 samples at 2 and 3 hours after injection, using the formula CLtr = 4.52 + 0.84CL1c - 0.00080(CL1c)2 (R2 = .97). Similar relationships were found when sampling at 2 and 4 hours or at 2, 3 and 4 hours after injection, whereas predictions from the 3- and 4-hour estimates were not optimal (R2 = .79). The 2-sample methods for calculating GFR/ECFV generally produced unreliable predictions of the complete curve GFR/ECFV values. For some dogs, the choice of standardization procedure substantially changed the apparent level of renal function relative to other dogs in the study. We conclude that by applying an appropriate correction formula, GFR may be estimated using 2 blood samples at 2 and 3, or 2 and 4 hours after injection of iohexol when renal function is normal or moderately reduced. The method of standardizing the analysis with respect to body size may influence interpretation of the results substantially.

Glomerular filtration rate (GFR) is estimated by means of clearance, defined as the volume of plasma that has been cleared of a particular substance per unit time. Glomerular filtration rate may be estimated by measuring the renal clearance of a filtration marker using data from both urine and plasma or by plasma clearance using only plasma data. Several alternative pharmacokinetic models are used for the calculation of clearance using various filtration markers with slightly different pharmacokinetic properties. The purpose of this article is to discuss how the choice of marker and pharmacokinetic model may influence estimated GFR values and to elucidate commonly used methods and reported GFR values in the dog.