Hypercalcemia and calcium oxalate urolithiasis in cats: a report of five cases.

Five cats that presented for signs of lower urinary tract disease (i.e., pollakiuria and hematuria) secondary to a calcium oxalate urolithiasis are presented. On evaluation, all five cats had elevations of both serum ionized as well as total serum calcium. The hypercalcemia resolved after discontinuation of urinary acidifying therapy or a dietary change, or both.     

Hypercalcemia in cats: a retrospective study of 71 cases (1991-1997)

A retrospective study was conducted to characterize the diseases, clinical findings, and clinicopathologic and ultrasonographic findings associated with hypercalcemia (serum calcium concentration >11 mg/dL) in 71 cats presented to North Carolina State University Veterinary Teaching Hospital. The 3 most common diagnoses were neoplasia (n = 21), renal failure (n = 18), and urolithiasis (n = 11). Primary hyperparathyroidism was diagnosed in 4 cats. Lymphoma and squamous cell carcinoma were the most frequently diagnosed tumors. Calcium oxalate uroliths were diagnosed in 8 of 11 cats with urolithiasis. Cats with neoplasia had a higher serum calcium concentration (13.5 ± 2.5 mg/dL) than cats with renal failure or urolithiasis and renal failure (11.5 ± 0.4 mg/dL; P <.03). Serum phosphorus concentration was higher in cats with renal failure than in cats with neoplasia ( P < .004). Despite the fact that the majority of cats with uroliths were azotemic, their serum urea nitrogen and creatinine concentrations and urine specific gravity differed from that of cats with renal failure. Additional studies are warranted to determine the underlying disease mechanism in the cats we identified with hypercalcemia and urolithiasis. We also identified a small number of cats with diseases that are not commonly reported with hypercalcemia. Further studies are needed to determine whether an association exists between these diseases and hypercalcemia, as well as to characterize the underlying pathophysiologic mechanism for each disease process.     

Evaluation of urine and serum metabolites in miniature schnauzers with calcium oxalate urolithiasis.

To evaluate underlying causes of calcium oxalate urolithiasis, 24-hour excretion of urine metabolites was measured in 6 Miniature Schnauzers that formed calcium oxalate (CaOx) uroliths during periods when they were fed a standard diet and during periods when food was withheld. Serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D also were evaluated. Serum calcium concentrations were normal in all 6 affected Miniature Schnauzers; however, during diet consumption, mean 24-hour urinary excretion of calcium was significantly (P = 0.025) higher than calcium excretion when food was withheld. In 1 dog, urinary calcium excretion was lower during the period of food consumption, compared with the period when food was withheld. Compared with clinically normal Beagles, Miniature Schnauzers that formed CaOx uroliths excreted significantly greater quantities of calcium when food was consumed (P = 0.0004) and when food was withheld (P = 0.001). Miniature Schnauzers that formed CaOx uroliths excreted significantly less oxalate than clinically normal Beagles during fed (P = 0.028) and nonfed (P = 0.004) conditions. Affected Miniature Schnauzers also excreted abnormally high quantities of uric acid. Excretion of citrate was not different between Miniature Schnauzers with CaOx urolithiasis and clinically normal Beagles. In 5 of 6 Miniature Schnauzers with CaOx urolithiasis, concentrations of serum parathyroid hormone were similar to values from age- and gender-matched Miniature Schnauzers without uroliths. The concentration of serum parathyroid hormone in 1 dog was greater than 4 times the mean concentration of clinically normal Miniature Schnauzers. Mean serum concentrations of 1,25-dihydroxyvitamin D in Miniature Schnauzers with calcium oxalate urolithiasis were similar to concentrations of clinically normal Miniature Schnauzers.     

Calcium urolithiasis in two dogs with parathyroid adenomas

Primary hyperparathyroidism resulted in calcium urolith formation and calcium nephropathy in 2 dogs. Uroliths composed of calcium phosphate were surgically removed from the bladder of one dog 3 months after surgical removal of a parathyroid adenoma. Five years later, hypercalcemia and urolithiasis had not recurred. In a second dog, calcium oxalate renal and bladder uroliths remained unchanged in size at 11 months after removal of a parathyroid adenoma. The possibility of primary hyperparathyroidism should be considered in any dog with calcium urolithiasis.     

Associations between dry dietary factors and canine calcium oxalate uroliths

OBJECTIVE: To identify factors in dry diets associated with the occurrence of calcium oxalate (CaOx) uroliths in dogs. ANIMALS: 600 dogs with CaOx uroliths and 898 dogs without urinary tract diseases. PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: Compared with diets with the highest concentrations of sodium, dry diets with the lowest concentrations of sodium, phosphorus, calcium, chloride, protein, magnesium, or potassium were linearly associated with increased risk of CaOx urolith formation. Significant nonlinear associations between increased occurrence of CaOx uroliths and urine acidifying potential and low moisture content were observed. Significant nonlinear associations between decreased occurrence of CaOx uroliths and carbohydrate and fiber contents were observed. A significant association between the occurrence of CaOx uroliths and dietary fat was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dry diets formulated to contain high concentrations of protein, calcium, phosphorus, magnesium, sodium, potassium, and chloride may minimize formation of CaOx uroliths. In addition, comparison of risk and protective factors of various diet ingredients fed to dogs with CaOx uroliths suggests that although similar findings were observed in canned and dry formulations, in general, greater risk is associated with dry formulations. However, before these hypotheses about dietary modifications are adopted by food manufacturers, they must be investigated by use of appropriately designed clinical studies of dogs with CaOx urolithiasis.     

Association between dietary factors and calcium oxalate and magnesium ammonium phosphate urolithiasis in cats.

OBJECTIVE: To identify dietary factors associated with the increase in occurrence of calcium oxalate (CaOx) uroliths and the decrease in occurrence of magnesium ammonium phosphate (MAP) uroliths in cats. DESIGN: Case-control study. ANIMALS: 173 cats with CaOx uroliths, 290 cats with MAP uroliths, and 827 cats without any urinary tract diseases. PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: Cats fed diets low in sodium or potassium or formulated to maximize urine acidity had an increased risk of developing CaOx uroliths but a decreased risk of developing MAP uroliths. Additionally, compared with the lowest contents, diets with the highest moisture or protein contents and with moderate magnesium, phosphorus, or calcium contents were associated with decreased risk of CaOx urolith formation. In contrast, diets with moderate fat or carbohydrate contents were associated with increased risk of CaOx urolith formation. Diets with the highest magnesium, phosphorus, calcium, chloride, or fiber contents and moderate protein content were associated with increased risk of MAP urolith formation. On the other hand, diets with the highest fat content were associated with decreased risk of MAP urolith formation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that diets formulated to contain higher protein, sodium, potassium, moisture, calcium, phosphorus, and magnesium contents and with decreased urine acidifying potential may minimize formation of CaOx uroliths in cats. Diets formulated to contain higher fat content and lower protein and potassium contents and with increased urine acidifying potential may minimize formation of MAP uroliths.     

Evaluation of urinary and serum metabolites in Asian small-clawed otters (Aonyx cinerea) with calcium oxalate urolithiasis.

Baseline renal function data was collected during 24-hr periods of feeding and fasting from three male and three female adult Asian small-clawed otters (Aonyx cinerea) with calcium oxalate urolithiasis. Urine was analyzed for calcium, phosphorus, and oxalate, and urinalyses were performed. There was no evidence of glucosuria, which has been previously reported in Asian small-clawed otters with urolithiasis. Urinary oxalate levels were quite high when compared with those of dogs and humans without uroliths, and the ratio of urinary oxalate to calcium was close to 1:1 during periods of food consumption. There was no significant difference in urinary oxalate excretion between the fed and fasting states. Urinary calcium excretion was five times greater during feeding than during fasting. Calcium levels were higher in the otters than those reported for dogs without uroliths but were similar to those for normal humans. Water consumption and urine production were significantly higher during periods of food consumption. Serum chemistry analyses and electrolyte levels were also determined. There was no evidence of hypercalcemia. Fractional clearance of calcium and phosphorus and endogenous creatinine clearance were significantly higher during food consumption than during fasting. Parathyroid hormone levels were similar to those reported for dogs and cats. Serum 25-hydroxy-vitamin D was slightly lower in the otters than in dogs.     

The effect of urine acidification on calcium oxalate relative supersaturation in cats

There is an apparent reciprocal relationship between magnesium ammonium phosphate (MAP, struvite) and calcium oxalate (CaOx) urolithiasis incidence rate in cats. The number of struvite uroliths submitted for analysis over the past 35 years has been decreasing, with an increase in CaOx urolith submissions. Commercial diets aimed to dissolve struvite uroliths are typically acidified, and it has been suggested that dietary acidification increases urinary calcium excretion and the risk of CaOx crystallization. The objective of this study was to assess the effect of urine acidification on the relative supersaturation (RSS) of CaOx in cats, as a representation of crystallization risk. Four diets were extruded to contain identical nutrient contents, but with gradual acidification (0, 0.6, 1.3 and 1.9% sodium bisulphate substituted sodium chloride in diets A, B, C and D respectively). Thirteen adult cats were fed each diet sequentially for a minimum of 10 days. Average urine pH was 6.4, 6.2, 6.0 and 5.9 on diets A, B, C and D respectively (p < 0.0001). Struvite RSS decreased on diets inducing more acidic urine pH (p < 0.0001). Urinary calcium excretion and concentration increased with diets inducing lower urine pH (p < 0.0001), but oxalate excretion and concentration decreased (p < 0.001). CaOx RSS was not different between diets (p = 0.63). These results suggest that a lower diet base excess and resulting urine pH to support struvite dissolution do not increase the risk for CaOx crystallization in the range of urine pH representative of most commercial feline diets. Long-term studies are needed to confirm this.     

Medical dissolution of feline struvite urocystoliths

The efficacy of a diet designed to facilitate dissolution of feline magnesium ammonium phosphate (struvite) uroliths was evaluated in 30 cases of urolithiasis, sterile struvite uroliths dissolved in a mean of 36 days after initiation of dietary treatment. In 5 cases of urolithiasis, struvite urocystoliths associated with urease-negative bacterial urinary tract infection dissolved in a mean of 23 days after initiation of dietary and antimicrobial treatment. In 3 cases of urolithiasis, struvite urocystoliths associated with urease-positive staphylococcal urinary tract infection dissolved in a mean of 79 days after initiation of dietary and antimicrobial treatment. Dissolution of uroliths in cats fed the treatment diet was associated with concomitant remission of dysuria, hematuria, and pyuria, and reduction in urine pH and struvite crystalluria. In one case, a urocystolith composed of 100% ammonium urate, and in another case, a urolith composed of 60% calcium phosphate, 20% calcium oxalate, and 20% magnesium ammonium phosphate did not dissolve.     

Effect of dietary phosphoric acid supplementation on acid-base balance and mineral and bone metabolism in adult cats.

Experimental evidence indicates that maintenance of urinary pH < or = 6.4 is the single most effective means of preventing feline struvite crystalluria or urolithiasis of noninfectious causes. This may be accomplished by dietary acidification, but must be moderated to avoid potential adverse effects of excessive acidification, including bone demineralization, negative calcium balance, potassium depletion, and renal disease. Effects of chronic dietary phosphoric acid supplementation on acid-base balance and on mineral and bone metabolism were investigated in adult, domestic cats. One group of 6 cats was fed a basal, naturally acidifying diet without added acidifiers, and another group of 6 cats was fed 1.7% dietary phosphoric acid. Changes observed during 12 months of study included development of noncompensated metabolic acidosis, increased urinary calcium excretion, and lower but positive calcium balance in cats of both groups. Urinary pH decreased in cats of both groups, but was significantly (P < 0.05) and consistently maintained < or = 6.4 in cats given dietary phosphoric acid. Urinary phosphorus excretion increased in cats of both groups, but was significantly (P < 0.05) greater in phosphoric acid-supplemented cats, leading to lower overall phosphorus balance as well. Potassium balance decreased in cats of both groups, but was only transiently negative in the phosphoric acid-supplemented cats midway through the study, and normalized at positive values thereafter. Plasma taurine concentration was not affected by dietary acidification, and remained well within the acceptable reference range for taurine metabolism. Double labeling of bone in vivo with fluorescent markers was followed by bone biopsy and histomorphometric measurement of several static and dynamic variables of bone formation. Overall indices of bone formation decreased in cats of both groups with age and confinement, but were not affected by dietary phosphoric acid supplementation. Dietary supplementation with phosphoric acid used as the principal inorganic P source to achieve moderate and stable degree of urinary acidification, did not appear over the course of 1 year, to have induced adverse effects on mineral, bone, or taurine balance in these adult domestic cats.     

Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure

BACKGROUND: Chronic renal failure is complicated by secondary hyperparathyroidism, which traditionally has been controlled by dietary restriction of phosphorus and administration of phosphorus binders. Early treatment of patients with chronic renal failure with calcitriol may be indicated because once established, parathyroid gland hyperplasia does not readily resolve with therapy. HYPOTHESIS: Daily and intermittent dosing of calcitriol will decrease plasma parathyroid hormone concentration in normal cats and cats with chronic renal failure without causing ionized hypercalcemia. ANIMALS: Ten normal cats; 10 cats with chronic renal failure. METHODS: Phase 1 was daily calcitriol administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout period separated phases 1 and 2. Before each phase, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of both phases, serum ionized calcium concentrations were measured. On the last day of both phases, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured 0, 2, 4, and 6 hours after calcitriol administration. RESULTS: Overall, serum parathyroid hormone concentrations were significantly higher in cats with chronic renal failure than in normal cats (P = .022), but serum parathyroid hormone concentrations for both normal cats and cats with chronic renal failure were not significantly different before and after 14 days of treatment with calcitriol, regardless of whether calcitriol was administered daily or intermittently. Adverse effects of calcitriol administration (specifically ionized hypercalcemia) were not seen in either feline group during either phase of the study over the 3-day evaluation after calcitriol administration was initiated. CONCLUSIONS AND CLINICAL IMPORTANCE: At the dosages used, calcitriol treatment did not result in significant differences in serum parathyroid hormone concentrations before and after treatment in both normal cats and cats with chronic renal failure. With these dosages, adverse affects of calcitriol administration were not seen. Potential reasons for lack of apparent effect include small sample size, insufficient duration of study, insufficient dosage of calcitriol, problems with formulation or administration of calcitriol, and variable gastrointestinal absorption of calcitriol.     

Canine calcium oxalate urolithiasis. Case-based applications of therapeutic principles.

The case study presented here illustrates the diagnosis and management of calcium oxalate urolithiasis in a Bichon Frise, a breed at increased risk for this type of stone. If the Bichon Frise had persistent hypercalcemia, we would have evaluated serum concentrations of ionized calcium, parathyroid hormone, and vitamin D to identify an underlying cause. Because his urine was alkaline, additional potassium citrate was not provided. Likewise, as a fortified diet was fed to him, vitamin B6 therapy was not considered. This case study illustrates the benefits of radiographic evaluation immediately following surgery and during follow-up examinations. If we had postponed radiographs until the patient developed clinical signs, additional surgical procedures may have been required.     

Substitution of dietary calcium chloride for calcium carbonate reduces urinary ph and urinary phosphorus excretion in adult cats

Summary

In a 4×4‐vvk cross‐over study, eight adult cats were given four moist diets containing identical amounts of calcium (13.9 mmol/MJ) but with different ratios of calcium carbonate to calcium chloride, the calcium salts providing half of the total dietary calcium. Increasing amounts of calcium chloride were substituted for equimolar amounts of calcium carbonate. Higher intakes of calcium chloride caused significantly lower pH values in postprandial and 24‐h urine samples. The urinary excretion of ammonium and titratable acid rose with increasing calcium chloride intake. The urinary concentrations of calcium and magnesium were not affected by the type of calcium salt, but the urinary excretion and concentration of phosphorus were significantly depressed when the amount of calcium chloride in the diet was increased. The results are discussed in the context of dietary prevention of and therapy for struvite urolithiasis in cats.     

Effects of diet on urine composition of cats with calcium oxalate urolithiasis

Ten client-owned cats with calcium oxalate (CaOx) urolithiasis were evaluated to determine the effect of diet on urine CaOx saturation. Two dietary treatments were evaluated in each cat: the diet consumed just prior to urolith detection and a canned diet formulated to prevent CaOx uroliths. This study revealed that hypercalciuria is a consistent abnormality in cats with CaOx urolith formation. When urolith-forming cats consumed a diet formulated to prevent urolith formation, activity product ratios for CaOx (which estimate the degree to which urine is saturated with CaOx) were significantly lower. These results suggest that consumption of an appropriately formulated urolith-prevention diet will reduce recurrence of CaOx urolithiasis.     

Effect of diet on struvite activity product in feline urine

Groups of male specific-pathogen-free cats were fed a basal, purified diet (A), with or without 0.45% added magnesium (MgCl2, diet B; MgO, diet C) or 1 of 2 commercial diets (D,E). Urine samples collected for 48 hours after 2 weeks of feeding were analyzed for calcium, magnesium, sodium, potassium, ammonium, sulfate, phosphate, oxalate, and citrate content. Concentrations were used to calculate the negative logarithm of the struvite activity product (pSAP), using a microcomputer-based program for calculation of supersaturation of the urine with crystal solutes. The pSAP value for all samples also was hand-calculated by use of an equation. Consumption of diet B caused a significant (P less than 0.05) increase in urine calcium concentration. Total urine phosphate concentration was lower in urine from cats fed diets A, B, or C than in urine from cats fed diets D or E. For the various diets, urine PO4(-3) was: 5.3 microM for diet A; 6.3 microM for diet C; 0.9 microM for diet E; 36 nM for diet D, and 0.5 nM for diet B. Consumption of diets B and C caused significant increases in urine magnesium concentration (53.1 nM and 49.1 mM, respectively). Ammonium ion concentration was highest in urine from cats fed diets B and D, 116.2 mM and 100.3 mM, respectively. When the pSAP, hand-calculated assuming ionic strength u = 0.2, was regressed on that calculated by use of the microcomputer program, the coefficient of determination was 0.96 (P less than or equal to 0.01).     

Effects of dietary cysteine on blood sulfur amino acid, glutathione, and malondialdehyde concentrations in cats

OBJECTIVE: To determine effects of dietary cysteine on blood sulfur amino acids (SAA), reduced glutathione (GSH), oxidized glutathione (GSSG), and malondialdehyde (MDA) concentrations in cats. ANIMALS: 12 healthy adult cats. PROCEDURE: Cats were fed diets with a nominal (0.50 g/100 g dry matter [DM]), moderate (1.00 g/100 g DM), or high (1.50 g/100 g DM) cysteine content in a 3 X 3 Latin square design with blocks of 8 weeks' duration. Venous blood samples were collected after each diet had been fed for 4 and 8 weeks, and a CBC and serum biochemical analyses were performed; poikilocyte, reticulocyte, and Heinz body counts were determined; and MDA, GSH, GSSG, and SAA concentrations were measured. RESULTS: Blood cysteine and MDA concentrations were not significantly affected by dietary cysteine content. Blood methionine, homocysteine, and GSSG concentrations were significantly increased when cats consumed the high cysteine content diet but not when they consumed the moderate cysteine content diet, compared with concentrations obtained when cats consumed the nominal cysteine content diet. Blood GSH concentrations were significantly increased when cats consumed the moderate or high cysteine content diet. CONCLUSIONS: Increased dietary cysteine content promotes higher blood methionine, homocysteine, GSH, and GSSG concentrations in healthy cats. CLINICAL RELEVANCE: Supplemental dietary cysteine may be indicated to promote glutathione synthesis and ameliorate adverse effects of oxidative damage induced by disease or drugs.     

The relative effects of supplemental dietary calcium and oxalate on urine composition and calcium oxalate relative supersaturation in healthy adult dogs

The aim of this study was to establish the relative effects of dietary calcium and oxalate (in the form of oxalic acid) on the composition of urine produced by healthy adult Cairn Terriers and Miniature Schnauzers. A nutritionally complete dry dog food was fed to 7 dogs (4 Cairn terriers and 3 Miniature schnauzers) for 24 weeks. The dogs were fed the diet alone, or supplemented with six different combinations of dietary calcium (as carbonate and sulphate) and oxalate (as oxalic acid) commonly found in dry commercially prepared dog foods. Urine pH, volume, specific gravity, and concentrations of 12 analytes were measured for each dog; urinary relative supersaturation (RSS) with calcium oxalate (CaOx) was calculated from these values. The effects of supplemental calcium and oxalate were established using two-way analysis of variance and multiple range tests (least significant difference); P<0.05 was considered significant. The lowest level of dietary calcium and oxalate resulted in the lowest CaOx RSS. The high calcium, low oxalate diet resulted in the highest CaOx RSS, a low calcium diet with increased dietary oxalate also tended to increase CaOx RSS although results were highly variable. Urinary calcium concentration increased significantly with dietary calcium; urinary oxalate increased, although inconsistently, with dietary oxalic acid only when dietary calcium was low. Measures to reduce both calcium and oxalate should be considered when implementing dietary changes to reduce the risk of calcium oxalate formation in dogs. A reduction in dietary calcium without a concomitant decrease in dietary oxalate may increase the risk of CaOx crystallisation in susceptible dogs.     

Vitamin D toxicity. Initial site and mode of action

Two groups of weanling pigs, injected with 45Ca, were fed diets containing optimal calcium and phosphorus, and vitamin D3 at 1320 IU/kg feed in the control group, and 825,000 IU/kg feed in the test group. The groups were further subdivided with 2 pigs in each subgroup, with survival times of 1, 2, 3, 4, 7, and 14 days. Pigs fed the high level of vitamin D3 lost weight and anorexia, weakness, rough hair coat and labored breathing were observed. Hypercalcemia began at 12 hours and progressed rapidly after 2 days. Radioisotope sutdies interpreted in the light of histopathologic findings indicated that bone was the primary source of increased plasma calcium. Calcium was released at a rapid rate into blood from prelabeled bone which was undergoing necrosis; it was also removed from blood and deposited into bone at a slower rate due to decreased apposition. Histopathologic examination of bones from test pigs showed regressive changes in the osteocytes, chondrocytes and osteoblasts which bean within 1 day of treatment and resulted in evidence osteopenia within 7 days. Arrested osteocytic osteolysis led to the appearance of cementing lines and to chondroid core retention. Further regressive changes in the osteocytes resulted in osteocytic death and osteonecrosis with subsequent osteoclasia and osteopenia. Retardation and arrest of cartilage maturation as well as osteoblastic deficiency contributed to the osteopenia. The osteopenia was further evidenced by decreased specific gravity and ash content per unit volume of humerus. The initial negative effect on the osteocytes, chondrocytes and osteoblasts is attributed to a direct toxic effect of excessive dietary vitamin D3 since hypoparathyroidism and hypercalcitoninism, which occur secondarily to hypercalcemia, could not account for the rapid appearance of this effect, nor are they known to induce osteocytic death. The release of bone calcium and the resulting hypercalcemia in vitamin D3 toxicosis is therefore due to a direct toxic effect of the vitamin, or its metabolites, on the osteocyte resulting in osteonecrosis. It is not due to increased resorption as has been reported previously from both in vivo and in vitro investigations. Degeneration, with subsequent inflammation, but without calcification, was observed in the kidneys and in the lungs. Epithelial cells, basement membranes, and smooth muscle were affected. This conclusively demonstrates that degeneration is the primary soft tissue lesion in vitamin D3 toxicosis, and that the subsequent calcification is therefore dystrophic. Degenerative changes occurred in the parathyroid glands within 1 day of treatment resulting in necrosis, inflammation and atrophy within 4 days. Relative fibrosis was seen as the parenchyma receded. The parathyroid gland changes were considered a direct effect of vitamin D3 toxicity since they occurred with only mild hypercalcemia and since necrosis of parathyroid cells has not been demonstrated with hypercalcemia either in vivo or in vitro.     

Detection of parathyroid hormone-related protein in cats with humoral hypercalcemia of malignancy

Background — Increased serum parathyroid hormone‐related peptide (PTHrP) concentration is used to diagnose humoral hypercalcemia of malignancy (HHM) in humans and animals. A commercially available assay for human PTHrP has diagnostic utility in the dog, but has not been assessed in cats. Objectives — The goals of this study were to determine serum or plasma levels of PTHrP in a population of hypercalcemic cats and to determine whether increased PTHrP concentration was associated with malignancy. In addition, we validated immunoradiometric assays (IRMAs) for intact parathormone (iPTH) and PTHrP for use with feline samples. Methods — A retrospective analysis of iPTH and PTHrP results from 322 hypercalcemic cats (ionized calcium concentration >1.4 mmol/L) was performed. Immunoassays for human iPTH and PTHrP (residues 1–84) were validated using standard methods, and reference intervals were calculated using values from 31 healthy adult cats. Hypercalcemic cats were classified as parathyroid‐independent (iPTH <2.3 pmol/L), equivocal (iPTH 2.3–4.6 pmol/L), or parathyroid‐dependent (iPTH >4.6 pmol/L). Seven cats with detectable or increased PTHrP concentrations were evaluated further for underlying disease. Formalin‐fixed neoplastic tissues were immunohistochemically stained using rabbit antibody to human midregion PTHrP. Results — Assays for iPTH and PTHrP showed acceptable precision for feline samples. The reference interval for iPTH was 0.8–4.6 pmol/L and for PTHrP was <1.5 pmol/L. The majority of hypercalcemic cats (263/322, 81.7%) were parathyroid‐independent, with fewer cats in the equivocal (32/322,9.9%) and parathyroid‐dependent (27/322,8.4%) groups. In 31 (9.6%) cats, PTHrP concentration was >1.5 pmol/L (range 1.5–26.6 pmol/L). All 7 cats for which follow‐up information was available had HHM; 6 had carcinomas (4 lung carcinomas, 1 undifferentiated carcinoma, 1 thyroid carcinoma) and 1 had lymphoma. All tumors had mild to moderate positive staining for PTHrP; however, lung carcinomas from normocalcemic cats also stained positive. Conclusions — Human IRMA for PTHrP (1–84) can be used to measure PTHrP in cats. Malignancies, particularly carcinomas, appear to secrete PTHrP and induce HHM in this species. Immunohistochemistry alone cannot predict the occurrence of HHM in cats.