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PHOSPHATEMIA

A ROUNDTABLE D ISCUSS ION

MANAGEMENTIN THE TREATMENTOF CHRONIC KIDNEY DISEASE

Dr. Jonathan Elliott: Today we willdiscuss an old-fashioned kidneyproblem: disorders of mineral bal-ance and phosphate. One of ourgoals is to build a consensus on theimportance of phosphate and para-thyroid hormone (PTH); we’ll debatewhether phosphate, PTH, or a com-bination of the two is important inkidney disease. A second objective isto provide treatment guidelines forhyperphosphatemia and hyperpara-thyroidism, indicating the quality ofthe evidence supporting the guide-lines. We will also identify areaswhere new research is warranted.____________________________

Pathophysiology of renal secondary

hyperparathyroidism____________________________

Elliott: Let’s begin by consideringthe pathophysiology of secondaryrenal hyperparathyroidism and therole of phosphate. Regulation of theconcentration of calcium and phos-phate in extracellular fluid involvesthe intestines, bones, kidneys, and

the movement of calcium and phos-phate between intracellular andextracellular fluid. The bones’ mas-sive store of bound calcium andphosphate is released or replenishedto protect the animal against a lackor excess of calcium and phosphatein extracellular fluid, includingblood. Hormones regulate this move-ment. When you study a patient’scomplex endocrine system by evalu-ating a blood sample, it’s difficult tounderstand what’s occurring in thisdynamic system—many differentfactors can influence each other(Figure 1, page 4). For example, adecreased ionized calcium concentra-tion and an increased phosphate con-centration in the extracellular fluidstimulate PTH secretion, and PTHincreases the release of calcium andphosphate from the bones. PTH alsostimulates the kidneys to producemore vitamin D, which increases cal-cium and phosphate absorption fromthe intestine. Phosphate and calciumare released from the bone to defendagainst hypocalcemia, and along

with PTH and vitamin D, they influ-ence the kidneys such that calciumis retained and phosphate is excreted.Vitamin D feedback inhibits PTHsynthesis. It also ensures that somenutritional calcium replenishes thatwhich came out of the bone. So PTHand vitamin D together are neededfor calcium to be released from andreplenished into the bones.

Let’s look at the Kidney DiseaseOutcomes Quality Initiative (KDOQI)guidelines in human medicine.KDOQI is an educational initiative ofthe U.S. National Kidney Foundation;the aim is to improve the quality ofcare of human patients with kidneydisease through the development ofscientifically rigorous guidelinesbased on a critical appraisal of theavailable evidence. These guidelinesmaintain that phosphate retentionoccurs early in the course of chronickidney disease, probably duringKDOQI stage I but certainly byKDOQI stage II (Table 1, page 5).This does not mean that the serumphosphate concentration is elevated

Gregory F. Grauer,DVM, MS, DACVIM

Department of Clinical Sciences

College of Veterinary Medicine

Kansas State UniversityManhattan, Kansas

Herve Lefebvre,DVM, PhD, DECVPT

Department of Clinical Sciences

National Veterinary School

Toulouse, France

Maria Josefa Fernandezdel Palacio, DVM, PhD,DECVIM-CA (cardiology)

Department of Animal Medicine and Surgery

Veterinary SchoolUniversity of MurciaMurcia, Spain

ModeratorJonathan Elliott, MA,

Vet MB, PhD, Cert SAC, DECVPT, MRCVS

Department of Veterinary Basic Sciences

Royal Veterinary CollegeUniversity of LondonLondon, England

ParticipantsScott A. Brown, VMD,

PhD, DACVIMDepartment of Small Animal

Medicine and SurgeryCollege of Veterinary MedicineUniversity of GeorgiaAthens, Georgia

Larry D. Cowgill, DVM, PhD, DACVIM

Department of Medicine and Epidemiology

School of Veterinary MedicineUniversity of California-DavisDavis, CaliforniaUniversity of California

Veterinary Medical CenterSan Diego, California

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PHOSPHATEMIAMANAGEMENT

IN THE TREATMENTOF CHRONIC KIDNEY DISEASE

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at that time; in fact, the serum phos-phate concentration may actually benormal or low. But whenever there isa reduction in the glomerular filtrationrate (GFR), whole-body phosphateretention is occurring. This phosphateretention is not the only contributorto hyperparathyroidism; the PTHconcentration starts to rise when theGFR is 50% of normal or below.

Phosphate is filtered and partiallyreabsorbed in the proximal tubule.The only way to excrete more is toreduce the amount that is reabsorbedin the proximal tubule. This is con-trolled by PTH, which reduces thetransport maximum of phosphate inthe proximal tubule and can causeup to 70% of the filtered load to beexcreted in the urine. However, onceGFR becomes limited (less than50% of normal) and dietary phos-phate remains the same, phosphatewill be retained in the body as intakeexceeds the capacity of the kidneysto excrete phosphate. PTH secretionthen becomes maladaptive as itreleases more phosphate from thebone. Because the kidneys cannotexcrete this phosphate, it accumu-lates in cells and extracellular fluid.The logical way we can address thisproblem and restore the balance isby reducing phosphate intake.

Secondary renal hyperparathy-roidism is an extremely commonfinding in chronic kidney disease;it is evident early in the disease syn-drome. Phosphate retention plays animportant role in its genesis. Evi-dence from human medicine shows

that this phenomenon decreases thequality of life and increases the riskof mortality. ____________________________

The role of PTH and mineral balance

in chronic kidney disease ____________________________

Elliott: The questions I have are: IsPTH responsible for this detrimentaleffect, or is the phosphate overloaddetrimental? Perhaps PTH is just agood indicator of phosphate overload.

How important is this syndrome incausing progressive renal injury instages I to III of chronic kidneydisease, using the InternationalRenal Interest Society (IRIS) classifi-cation? And how does this syndromerelate to other causes of progressiverenal injury, such as hypertensionand proteinuria?

Dr. Larry Cowgill: Is phosphate orPTH the bad guy? We have dealt withthe problem of secondary hyperpara-thyroidism from the human perspec-tive, in which metabolic bone diseaseis one of the major clinical problemsassociated with this syndrome.

In the majority of veterinary pa-tients, I think renal osteodystrophyisn’t clinically manifested enough towarrant therapeutic management. Wemay have to shift our perspective onhyperparathyroidism and hyperphos-phatemia from the human concept towhat is relevant in our patients.

Elliott: Renal osteodystrophydefinitely occurs. If you see theseanimals late enough in the diseaseprocess, you can see it radiographi-cally, which presumably means thatit has occurred for quite some time.

Cowgill: But it generally is not clin-ically manifested.

Dr. Astrid van Dongen: Eventhough practitioners don’t see thesigns, they shouldn’t just forget aboutthe problem. We may not see bone-related disease that often in renalpatients, but when we find other evi-dence of calcium-phosphate imbal-ance, there is something wrong thatwould be worthwhile to normalize.

Cowgill: If we can’t attribute anyclinical significance to hyperparathy-roidism in animals with chronickidney disease—other than deve-loping bone disease at a late stage—

Astrid van Dongen, DVM, RNVA (specialist CA—internal medicine)

Department of Internal Medicine

University of UtrechtUtrecht, The Netherlands

Bernhard Gerber, Dr. med. vet., DACVIM,DECVIM-CA

Clinic for Small Animal Internal Medicine

Vetsuisse FacilityUniversity of ZurichZurich, Switzerland

David Polzin, DVM,PhD, DACVIM

Department of Veterinary Clinical Sciences

College of Veterinary Medicine

University of MinnesotaSt. Paul, Minnesota

Secondary renalhyperparathyroidism

is an extremelycommon finding in chronic kidney

disease; it isevident early in thedisease syndrome.

—Dr. Elliott

A ROUNDTABLE DISCUSSION

then maybe we don’t need to be asconcerned about it.

Elliott: The problem is that the twoare intrinsically linked. In my experi-ence, if you change phosphate levels,you change PTH levels.

Dr. David Polzin: I suspect there is a big difference there. Youcan have phosphate levels that,while within the normal range, areat the high end of the range, withPTH values remaining quite elevat-ed. I think it really matters whichone we focus on to influence theclinical outcome. If we base therapyon PTH, we have to prove thatthere’s a link between the clinicaloutcome and PTH. We know theclinical outcome is linked to phos-phate control.

Elliott: So the practical approach isto control phosphate. The difficultconcept to sell to practitioners is atwhat phosphate concentration theywill see benefits. Do we need moreclinical studies?

Dr. Scott Brown: Recent clinicalstudies from Minnesota have con-firmed the applicability of laboratorystudies of models to animals withspontaneous kidney disease.1,2

Further, we know that structural orfunctional progression in the remnantkidney model is directly related toserum phosphate concentration indogs and cats.3,4 It’s thus reasonableto argue that we should restrictphosphate or provide an intestinalphosphate binder to control theserum phosphate concentration. Andthere is enough evidence in other

species to suggest that “under con-trol” means a serum phosphate con-centration well within the normalrange or even in the bottom half ofthe normal range.

Elliott: Our experience in cats hasbeen if we can control phosphate,we can control PTH. To summarize,hyperphosphatemia related tochronic kidney disease warrantstreatment and can lead to secondaryrenal hyperparathyroidism throughPTH stimulation.

van Dongen: Practitioners shouldmeasure phosphate levels and adjusttheir therapy accordingly. But in anideal situation, PTH and vitamin Dlevels should be checked in additionto phosphate levels.

Dr. Maria Josefa Fernandez delPalacio: I agree with Dr. van Dongenthat for practitioners, it would bemore practical to measure phosphatelevels first because this parameter isusually included in the biochemicalpanels. As a second step, PTH meas-urements would be desirable.

Dr. Greg Grauer: On the scale of1 to 10, the quality of evidence forcontrolling hyperphosphatemia inchronic kidney disease is close to 10.We don’t have nearly the same levelof evidence for controlling PTH.

Cowgill: Despite this, I have a con-cern about this broad range of earlykidney disease occurring with a nor-mal serum phosphate concentration.The only indication that phosphatemetabolism is disordered at that dis-ease stage is probably the PTH,which could identify the need forphosphate restriction at an earlierdisease stage than the serum phos-phate concentration. I am concernedthat we are not seeing elevations inthe serum phosphate concentration

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IN THE TREATMENT OF CHRONIC KIDNEY DISEASE

1. The sequence of events following a decrease in extracellular ionized calcium. Forsimplicity, this schematic considers only calcium and does not refer to phosphate.

1. A decrease in extracellular fluid ionized calcium is sensed by calcium-sensingreceptors at the level of the parathyroid gland.

2. PTH is secreted into the blood.3. PTH acts on the bone and kidney and, via active vitamin D3 (1,25 D3), acts on

the intestine to increase extracellular fluid ionized calcium.4. The increase in ionized calcium and 1,25 D3 concentrations acts on the para-

thyroid gland to inhibit PTH secretion.5. Increased 1,25 D3, over a longer time period, allows the calcium coming into

the body from the intestines to replenish the bone stores with calcium.

Figure 1: Regulation of extracellular ionized calcium by theendocrine system

1

2

3

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PHOSPHATEMIA MANAGEMENT

until creatinine levels are 3.5 to 4mg/dl (310 to 360 µmol/l). Phosphatemanagement could be beneficial atan earlier stage, and practitionerswould miss this opportunity if theyjust focused on the serum phosphateconcentration. Monitoring serumPTH levels at IRIS stage II andprobably early stage III would likelybe beneficial.

Elliott: My concern is that practi-tioners tend to think that if phos-phate isn’t elevated, they don’t needto restrict it. They might feed a renaldiet anyway just because the creati-nine is elevated. They may misun-derstand the reason why diet bene-fits the individual animal—they maythink it helps because of decreasedprotein levels, but the decreased

phosphate levels in the diet alsohelp. Another concern is that asphosphate starts to increase, theyshould target the lower end of thereference range. Practitioners needto recognize that a phosphate in thenormal range could still be abnormalin renal patients.

Cowgill: Given the lack of a strongcorrelation between hyperparathy-roidism and clinical signs relative toanimals with kidney disease, couldwe say that—at a minimum—PTHserves as a surrogate marker fordysregulation of mineral balance inthe face of a normal serum phos-phate concentration?

Dr. Herve Lefebvre: That’s a goodpoint. If the serum phosphate con-

centration is normal in animals withchronic kidney disease, I’d recom-mend assessing the PTH to confirmhyperparathyroidism.

Grauer: Clinical experience suggeststhat PTH levels can be elevated inearly chronic kidney disease beforethe onset of hyperphosphatemia. Butdo we have data showing that treat-ment of hyperparathyroidism at thisstage affects patient outcome?

Cowgill: We have lots of caninedata showing that in the early stageof disease, treating the phosphateimbalance with dietary reductioncorrects the hyperparathyroidism.5,6

So hyperparathyroidism can serve asa sensitive marker that the mineralbalance is abnormal.

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Stage Description GFR IRIS stage* Plasma creatinine** (KDOQI) (ml/min/1.73 m2)

I Kidney damage >90 I Cat: <1.6 mg/dlwith normal or (<140 µmol/l); adequate GFR Dog: <1.4 mg/dl

(<125 µmol/l)

II Kidney damage 60 to 89 I to early stage II Cat: 1.4 to 2.8 mg/dlwith mildly (140 to 249 µmol/l); decreased Dog: 1.4 to 2 mg/dlGFR (125 to 179 µmol/l)

III Moderately 30 to 59 Later stage II and stage III Cat: 2.9 to 5 mg/dldecreased GFR (250 to 439 µmol/l);

Dog: 2.1 to 5 mg/dl(180 to 439 µmol/l)

IV Severe reduction 15 to 29 IV Cat and dog: >5 mg/dlin GFR (>440 µmol/l)

V Kidney failure of <15 (or dialysis) Late stage IV Cat and dog:sufficient severity Not defined but to require renal >5 mg/dl (>440 µmol/l)replacement therapy (dialysis or transplant)

* The IRIS classification is based on plasma creatinine and the limitations of this system are recognized, particularly in precise definition ofkidney function in stages I to III.

** These creatinine concentration values are a guide based on expert opinion.

Table 1: Classification of kidney disease in KDOQI vs. IRIS stages

Brown: There is certainly correla-tive evidence that PTH may bedetrimental, but the confoundingproblem is that the PTH level is alsodirectly correlated to the degree ofphosphate imbalance. If we makeclinically relevant recommendations,the logical target is the serumphosphate concentration. To me, the first step is targeting the phos-phate level with appropriate dietarymaneuvers, rather than recommend-ing an ancillary test.

Polzin: The implication might bethat if you treat a patient appropriate-ly over an extended period of time,you could in fact just monitor theserum phosphate concentration.

Elliott: Yes, as long as you keep thephosphate in the optimal range.

Polzin: I don’t think we have proofof a cause and effect relationshipbetween PTH levels and progressionof kidney disease, but we dobetween phosphate intake andprogression. Another issue is thatI’m not sure it’s possible to identifythe phosphate level within IRISstage II, for example, that reliablynormalizes PTH levels. If weanswered that question, it would beeasier to focus on the phosphatelevel. Then you get into the issuethat is confronting the IRIS—we aresuggesting that phosphate should bebelow a number that is well withinthe normal range. We are essentiallychanging the normal range in therenal patient, which practitionerscan find confusing.

Grauer: Well, we’ve recentlychanged what we think is normaland abnormal for hypertension andproteinuria. Maybe we need to dothe same for creatinine and phos-phate concentrations.

So should practitioners initiate

dietary phosphate restriction beforethe onset of hyperphosphatemia?

Brown: There are data suggestingthat using a phosphate-restricted dietat IRIS stages II to III has a benefi-cial effect on clinical outcome.1,2

It’s important that we notbecome trapped in the concept thatevidence-based medicine means weonly use evidence from prospectiveclinical trials or that we not extra-polate results of human trials toanimals. Evidence-based medicinemeans we highly value randomized,placebo-based, blinded prospectiveclinical trials—but as nephrologistsand veterinarians, if we don’t haveapplicable prospective trials, we areobligated to rely on the best avail-able evidence. This is really whatevidence-based medicine means.Thus, if we have no clinical trialsbut we do have results from good,applicable model studies, we baseour decisions on those modelstudies. If we don’t have modelstudies in our species of interest,then we look at studies in otherspecies. Here, evidence in rodentsand people clearly shows somebenefit of phosphate restriction innormophosphatemic, early-stagekidney disease.

Polzin: That is an important point.Evidence-based medicine meanslooking at the best available evi-dence. If the best evidence is frompeople, we should use that.

Elliott: So our consensus is that weshould monitor the serum phosphateconcentration in animals with chron-ic kidney disease. We may also lookat PTH in animals that are normo-phosphatemic to see whether weneed to restrict phosphate. Thismight be a reasonable marker forphosphate and mineral imbalance.

____________________________Evidence from

experimental animal models and clinical cases____________________________

Brown: The data from multiplelaboratory studies on the relation-ship of phosphate to kidney diseaseare quite clear: Dietary phosphaterestriction, at least in IRIS stages IIand III, is protective of renal struc-ture, function, and survival.3,4

Polzin: A number of studies havebeen performed on dogs and catswith naturally occurring chronickidney disease. In these studies, thephosphate-restricted diets in bothdogs and cats were associated withsignificant improvement in survival.In a study examining the effect ofdiet on survival in dogs with IRISstages III and IV chronic kidneydisease, dogs consuming a phosphate-restricted diet survived approximate-ly three times longer than dogs fed astandard maintenance diet. Similarbeneficial effects have been observedin cats with stages II and III chronickidney disease.1,2,7

Cowgill: So these data indicate asurvival advantage for dietary phos-phate restriction, but the advantagewas independent of any change inthe serum phosphate concentration.

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Dietary phosphaterestriction, at least

in IRIS stages II and III, is

protective of renalstructure, function,

and survival.—Dr. Brown

The serum phosphate concentrationwas not a marker or predictor.

Polzin: Nor was PTH. What doesthis mean in terms of using phosphateor PTH as an endpoint for therapy?

Grauer: Well at one level, it con-founds things. But at the practical,everyday level, it creates a nicescenario. We don’t deal with renalfailure diets that are just sodium-reduced, omega-3 fatty acid-supplemented, alkalinized, protein-reduced, or phosphate-restricted. Weare looking at the whole package,and the whole package works.

Elliott: We need to remember that aphosphate in the top end of the refer-ence range* is probably not appropri-ate in IRIS stages II and III.

Cowgill: Just as creatinine at thetop of the normal range doesn’tmean that your patient is normal orthere aren’t consequences. Thiswhole concept of important para-meters being within the normalrange is a problem throughout allstages of kidney disease. Practition-ers could fail to recognize diseasebecause the levels are within thenormal range, when in fact the ani-mal has progressive disease. It is notuntil it extends out of the normalrange that they recognize it. If crea-

tinine and other blood values arenormal, they can recognize renaldisease by identifying other parame-ters that reflect alterations of renalstructure or function.

Polzin: So can we agree on theserum phosphorus target in chronicrenal disease?

Brown: I’d recommend a serumphosphate level of 2.5 to 4.5 mg/dl(0.81 to 1.45 mmol/l) for IRIS stageII, 2.5 to 5 mg/dl (0.81 to 1.61mmol/l) for stage III, and 2.5 to 6mg/dl (0.81 to 1.94 mmol/l) forstage IV.

____________________________Experience from human medicine____________________________

Elliott: Let’s now talk about guide-lines for human medicine. I think itwould be interesting to contrast thosewith the experiences and recommen-dations that practitioners make whenmanaging their patients.

To summarize available studyfindings, hyperphosphatemia is asso-ciated with morbidity and mortality inpeople with kidney disease. The evi-dence supports an association be-tween the serum phosphate concentra-tion, both above and below the refer-ence ranges, with poor outcomes.8 Sothe maintenance of a normal serumphosphate concentration is critical for

the prevention of abnormalities inPTH metabolism. The KDOQI guide-lines for the control of phosphate andPTH are presented in Table 2.

____________________________Effective treatment protocols____________________________

Grauer: Let’s look at how hyper-phosphatemia and hyperparathy-roidism should be managed inchronic kidney disease patients andhow we can monitor the effective-ness of treatment (see Q&A: Recom-mendations for serum phosphatemanagement in chronic kidney dis-ease, pages 8 to 9).

I’d suggest you start with a renalfailure diet, monitor the response,add phosphate binders (if needed),again monitor the response, andthen add calcitriol (at least in dogs)if you can’t reach your serum phos-phate concentration goals with theinitial treatments.

____________________________RENAL DIETS____________________________

van Dongen: The renal diet is dif-ferent from the maintenance diet inmore than one way. So the first stepin managing patients with chronickidney disease is to change the dietas much as possible before even con-sidering a phosphate binder. We haveevidence indicating that a completerenal diet with all its differences hasa better clinical outcome.

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KDOQI stage Recommended serum Recommended intact Strength of evidence forphosphate level PTH level serum phosphate and PTH*

III 2.7 to 4.6 mg/dl 35 to 70 pg/ml Opinion(0.87 to 1.48 mmol/l)

IV 2.7 to 4.6 mg/dl 70 to 110 pg/ml Opinion(0.87 to 1.48 mmol/l)

V 3.5 to 5.5 mg/dl 150 to 300 pg/ml Evidence(1.13 to 1.78 mmol/l)

* KDOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42(suppl 3):S1-S201.

Table 2: KDOQI recommendations for phosphate and PTH levels

* Laboratory reference ranges for serum phosphate in dogs and cats vary but can range from 1.8 to 6.2 mg/dl (0.6 to 2 mmol/l).The upper limit of the target range for all stages of chronic kidney disease are well within laboratory reference ranges for thereasons stated in the text.

Brown: In dogs and cats withchronic kidney disease, no one hascompared the efficacy of phosphatecontrol with a maintenance diet plusa phosphate binder to a phosphate-restricted prescription renal dietalone. While the results might besimilar, there are other nutritionalchanges in special diets, such aspotassium and alkali supplementa-tion, that make them preferable.

Because of the nature of the avail-able data, we don’t know if it’s justphosphate restriction that is bene-ficial in the clinical trials. I think it is the phosphate restriction partially,but it could be some combination ofdietary factors. To me a logical firststep—after the dog or cat is com-pletely evaluated diagnostically and

you establish that it has chronic kid-ney disease—is to recommend arenal diet. Then you follow it forseveral weeks to determine what ishappening to the serum phosphateconcentrations before you add aphosphate binder.

Elliott: We know that about 40% ofthe cats put on a renal diet will eithernot eat enough or not eat at all.2 Arewe recommending that these cats befed a standard maintenance diet plusphosphate binders?

Brown: Yes, but only as a last resortafter attempting to feed a renal diet.There are many other benefits to arenal diet, depending on the stage ofkidney disease. There is no doubt that

if an IRIS stage III or higher animalis given a high-protein diet, this sub-stantially increases its risk of experi-encing a uremic crisis. It is importantto recommend that the animal beintroduced to a renal diet in a verycontrolled and gradual manner. Someexperts also say there is a benefit tochanges in fatty acid, sodium, or pro-tein composition in the renal diets.

Cowgill: In your experience, are the40% of patients that won’t eat a renaldiet in a higher stage of chronic kid-ney disease?

Elliott: They tend to be cats thathave been fed a variety of foods. Ifthey’ve had prawns, then they justdon’t look at the renal diet.

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What should practitioners keep in mindwhen treating phosphate overload?

• This is a chronic treatment for stable chronic kidney diseasepatients.

• Stability of chronic kidney diseasepatients should be demonstrated byserial serum creatinine measure-ments for two to four weeks.Stability of serum phosphate con-centrations can also be establishedover this time.

• Benefits come from long-term con-trol of serum phosphate concentra-tion (for months to years).

• Acute problems in kidney diseasepatients (e.g., pyelonephritis, severehypertension) should be managedbefore introducing methods ofmanaging the serum phosphateconcentration.

When should chronic kidney diseasepatients receive treatment for phosphateoverload?Derangements in phosphate homeostasisare commonly associated with chronickidney disease even at early stages

because phosphate accumulates in thebody when the disease reduces the GFR.

The following recommendations are basedon treating phosphate overload with theobjective of maintaining the serum phosphateconcentration within the recommended range:

• In IRIS stages III and IV, a clinicalrenal diet is recommended for manyreasons, including controlling theserum phosphate concentration (IRIStreatment recommendations).

• In IRIS stage II, dietary phosphaterestriction might be considered evenif the serum phosphate concentra-tion is in the recommended targetrange if elevated serum PTH con-centrations are documented. How-ever, more research is necessarybefore specific recommendationscan be made on this issue. If serumPTH is not measured, do not restrictphosphate intake for patients withserum phosphate concentrations ofless than 4.5 mg/dl (1.45 mmol/l)(i.e., within the target range foranimals with IRIS stage II chronickidney disease).

What is the target serum phosphateconcentration that should be achievedwith treatment?The target serum phosphate level (two monthspost-treatment) and, therefore, the degree ofphosphate restriction required depend on theIRIS stage of chronic kidney disease:

Stage II—2.5 to 4.5 mg/dl (0.81 to 1.45 mmol/l)

Stage III—2.5 to 5 mg/dl (0.81 to 1.61 mmol/l)

Stage IV—2.5 to 6 mg/dl (0.81 to 1.94 mmol/l)

How should these targets be achievedand what monitoring procedures shouldbe applied?The serum phosphate concentration should be controlled by gradually intro-ducing a phosphate-restricted diet. Allcommercially available renal diets can be used to achieve phosphate restrictionbecause they are all relatively lower inphosphate than standard pet food diets.These renal diets should be introducedgradually over a period of seven days.The greater the proportion of the renal diet fed, the better.

Q&A: Recommendations for serum phosphate management in chronic kidney disease

Polzin: Cats that accept a renal dietgenerally do well on them. Most ofthese cats maintain body weight,and their hair coats and body condi-tions remain good. But problemsarise if they fail to consume an ade-quate number of calories. If youcombine lower protein intake withinadequate dietary intake, then youget into trouble.

Brown: Yes. Inadequate intake of a protein-restricted diet may posemore of a nutritional risk than inade-quate intake of a nonrestricted diet.This is probably true for many nutri-ents. But when addressing phosphatebalance only, there are alternatives toa renal diet. In early chronic kidneydisease, we have already suggested

that practitioners consider a dietmixture with intermediate levels ofprotein and phosphate plus a phos-phate binder if they are worriedabout hair coat or diet palatability.

Polzin: Studies in people havelooked at the effect of partial dietcompliance. They have documentedthat partial compliance is superior tononcompliance. In our trials in dogsand cats, we assumed that we’d getpartial compliance, so we toleratedup to 20% noncompliance. We keptdietary records, and most dogs andcats were at least 90% compliant.One way to address the noncompli-ance issue would be to recommendthat clients use as much of a renal-type diet as possible, so at least some

of the diet consumed is renal. Oursuccess rate is much higher thanyours, which in part reflects thatmore people in the United Statesfeed a commercial pet food than inGreat Britain. You could also formu-late a homemade renal diet if the petwould be more likely to eat it.

Grauer: How much difference isthere between the various renal dietsin regard to phosphate content?

Brown: I don’t see how you candistinguish them for a variety ofreasons. For one, depending on howthe phosphate level in the diet isexpressed and what the caloric con-tent of the diet is, it’s difficult to knowwhich diet really provides the lowest

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Patients should be reevaluated after fourweeks of dietary therapy. If the serumphosphate concentration is greater than 6mg/dl (1.94 mmol/l), introduce an intestinalphosphate binding agent, reevaluate afterfour weeks, and adjust the dose to achievethe target level for the stage of chronickidney disease.

If the serum phosphate concentration is lessthan or equal to 6 mg/dl (1.94 mmol/l) afterfour weeks, continue dietary therapy for fourmore weeks. If the target serum phosphateconcentration has not been achieved at thistime, introduce an intestinal phosphatebinder. Reassess after four weeks and adjustthe dose of phosphate binder to achieve thetarget phosphate concentration.

Once the target serum phosphate con-centration has been achieved, monitorevery two to four months to maintain thephosphate level within the desired range.As chronic kidney disease progresses,the degree of phosphate restriction, dosageof intestinal phosphate binding agent, orboth will need to increase. This occursdespite the fact that the target serumphosphate concentration increases aschronic kidney disease progresses fromIRIS stages II to IV.

What intestinal phosphate-bindingagents are available?The available binding agents are:

• Aluminium carbonate• Aluminium hydroxide• Aluminium oxide• Calcium carbonate (+/- chitosan)• Calcium acetate• Calcium citrate• Lanthanum carbonate• Sevelamer hydrochloride.

How should phosphate-binding agentsbe used?The following recommendations are fordosing:

• Starting dose should be 30 to 60mg/kg.

• Powdered and granular preparationsare recommended over liquids andgels, which might affect palatabilityof the diet.

• The binder must be mixed with thediet.

• Reassess serum phosphate concen-tration every four weeks.

• Increase dose to effect (doublingincrements to a maximum tolerabledose) and reassess.

• When using aluminium-containingbinders, drug-induced microcytosis,

muscular weakness, and encepha-lopathy are possible.

• Higher doses of the binder will berequired if the animal is consuminglow amounts of a renal diet (or adiet relatively higher in phosphate)and as the stage of chronic kidneydisease increases.

• Constipation is a potential complica-tion of higher doses of any of theavailable intestinal phosphate-binding agents.

What are the recommendations for theserum calcium concentration?Phosphate and calcium homeostasis areintrinsically linked—both are affected bychronic kidney disease as GFR decreases.Thus:

• Serum calcium concentrationsshould be monitored together withphosphate.

• If the total calcium concentration is elevated, assess ionized calciumconcentration.

• In cases where ionized calciumconcentrations are elevated, replacecalcium-containing phosphatebinders with alternatives (e.g., alu-minium hydroxide, lanthanum car-bonate, or sevelamer hydrochloride).

phosphate intake per kg of patient.The other variable is that phosphateavailability in these diets has neverbeen compared and dietary phytinlevels alter phosphate absorption con-siderably. Furthermore, we should becareful not to simply recommend aphosphate-restricted diet as the bestoption; we should clearly indicate thata diet formulated for chronic kidneydisease is our first preference.

Elliott: The renal diets are morethan phosphate-restricted; they haveother potential benefits, and for thiscategory of patient, they are allappropriate. So the renal diet is fedfor four weeks and is introducedgradually over one to two weeks bymixing it with the original diet andincreasing the proportion over time.Then the animal is reevaluated afterfour weeks.

____________________________PHOSPHATE BINDERS____________________________

Cowgill: Let’s discuss the manage-ment of patients that require morethan a renal diet to manage hyper-phosphatemia—patients that needphosphate binders. I think thebiggest failure in the managementof hyperphosphatemia in uremicanimals is not necessarily whichphosphate binder is prescribed buthow it is used. Veterinarians may nothave a good understanding of howthese drugs should be used; there isno standard dose. You dose to theoutcome that you want within rea-son. The dose is markedly depend-ent on the diet’s basal phosphatecontent and the timing of the medi-cation with the diet—all potentialcauses of treatment failure. Withdietary phosphate binders, the med-ication has to be physically coupledwith the diet.

Animals with kidney failure don’teat like young, healthy Labradors—they don’t eat all of their food in one

gulp. If you administer a pill and theanimal eats throughout the day, thereis no timing of medication with thediet—and no likelihood that thismedication will work. It will workbest if mixed with food, but only tothe extent that it doesn’t adulteratethe food so the animal will not con-sume it. Practitioners should recom-mend medications that are not fla-vored. Practitioners may not embracephosphate management because theydon’t understand how to effectivelyprescribe it and, therefore, don’t seeclinical benefits.

van Dongen: Practitioners alsoneed to be sure that they are dealingwith a patient with stable chronickidney disease. Sometimes it is noteasy to be sure about the nature ofkidney failure (e.g., acute, extra-renal, a combination, or complicatedby ascending infection) on initialconsultation. Rather, practitionersshould postpone phosphate manage-ment until initial treatment, results,and follow-up have confirmed thatthe renal patient is not deterioratingor improving rapidly, is capable ofmaintaining its fluid balance, and is

ingesting enough food. You cannotforget the basic steps.

Cowgill: I find it amazing howmany referrals I get for acute kidneyfailure. These patients often have aphosphate level approaching orexceeding 25 mg/dl (8.06 mmol/l)and are being treated with intestinalphosphate binders, despite the factthat the animals are not eating.

van Dongen: Or worse, sometimesan animal is referred for kidney dis-ease and a urinary tract infection isalso detected during the workup buturine was not checked before refer-ral. These initial steps are important.

Elliott: So our conclusion is thatphosphate binders are a long-termtreatment; they aren’t a quick fix.This treatment involves long-termphosphate control, which is impor-tant in managing patients withchronic kidney failure. And toensure a good outcome, practitionersneed to monitor phosphate levelsperiodically because these levels canincrease even if phosphate bindersare administered.

Cowgill: Historically, the way wehave dosed phosphate binders isintrinsically wrong. They should bedosed based on the amount of phos-phate in the diet, but we make blan-ket recommendations of 30 to 60mg/kg. We need to understand howmuch phosphate is in the diet andhow much phosphate binder—basedon its binding capacity—would tieup that phosphate. We know the con-tent of most of the diets animals eatthese days, so it’s possible to esti-mate the phosphate intake.

Elliott: We also want to encouragemonitoring the serum phosphateconcentration as part of long-termmonitoring of animals with chronic

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The biggest failure in the management ofhyperphosphatemiain uremic animalsis not necessarilywhich phosphate

binder is prescribed but how it is used.

—Dr. Cowgill

kidney disease, which helps us adjustthe dose to suit the individual patient.The other factor that influences doseis the stage of kidney disease.

Dr. Bernhard Gerber: What start-ing dose of phosphate binders shouldpractitioners recommend?

Grauer: Historically, aluminumhydroxide or calcium compoundshave been recommended, starting at30 mg/kg and increasing to 90 mg/kgor above as needed.

Polzin: Two important factors playa role in dosing. First, the dietaryphosphate level, even with the sameGFR, can profoundly alter the star-ting dose of phosphate binder. Thenthere is the concept of proportionalreduction in phosphate according tothe reduction of GFR, which in-volves the stage of kidney disease.So with an animal at a certain stageof chronic kidney disease on a partic-ular diet, you can estimate the phos-phate intake, which may lead you toa very different starting dose than thestandard recommendation. Is there away to use those two factors togetherto determine a dosing recommenda-tion? Again, practitioners can be-come frustrated quickly because thephosphate binder isn’t working—they may be looking too soon or thedosing is not optimal. For example,if you use a phosphate binder with astandard diet in an animal with fairlyadvanced kidney failure and you startwith a 30 mg/kg dose, you may seeno response at all. So we shouldprobably do a better job of linkingstarting dosage to the severity of thedisease and providing very explicitfollow-up recommendations.

Elliott: How stable is this animalbefore we start treatment? If you takeone pretreatment sample for theserum phosphate concentration and

a later posttreatment sample showsthat the phosphate has increased ordecreased, you don’t actually knowhow stable that animal was initially.The recommendation is to take twopretreatment samples to evaluatewhether this animal presentedbecause it suddenly deteriorated andif its second pretreatment sampleshows a further deterioration. Quiteoften, it has improved since the firstsample. Then you take a third sampleto see whether it really stabilized, andyou base your treatment on this.

Cowgill: There is no rationale foradding a phosphate binder until youhave exhausted the limits of dietaryphosphate reduction. As you tran-sition the animal to the diet, youhave the opportunity for two orthree serum phosphate measure-ments to determine the stability and baseline value.

Polzin: I’d be surprised if waitingtwo or three weeks to modifyphosphate levels would alter thedisease outcome. It makes sense toestablish the serum phosphate con-centration baseline for the patientfirst and then determine what to do.Again, you don’t want to makeabrupt diet changes as most dogsand cats won’t accept them. It maybe a couple of weeks to monthsbefore you can decide to add aphosphate binder. We don’t want to present this as an urgent thing.

Elliott: Are calcium-containing phos-phate binders and the risk of hyper-calcemia an issue in veterinary medi-cine like they are in human medicine?

Cowgill: First, I don’t think wehave necessarily excluded aluminumas an effective phosphate binder inanimals. We don’t know if animalshave the same historical problemswith aluminum as people. Do we

know that aluminum affects theneurologic system? Do we knowthat we have aluminum bone diseaseor aluminum toxicity? As you usehigher doses of aluminum-basedphosphate binders in animals withmore advanced disease, the likeli-hood of seeing aluminum toxicity isreal and needs to be monitored. Butat varying stages of chronic kidneydisease, you can also see definiteeffects of hypercalcemia fromcalcium-based binders.

Elliott: The problem I have is thataluminum-based binders have disap-peared from the pharmacy shelf.

Polzin: It is sometimes difficult forowners and practitioners to getaluminum-based phosphate bindersunless it is through a veterinary dis-tributor or university.

Cowgill: If you use an aluminumpowder, you can sprinkle it on thefood. I think gels are a disaster. Wehave ordered reagent-grade aluminumvery economically from suppliers,and you can provide that in a veryeasy form and mix it with canned orkibble foods. Aluminum hydroxidealso works very effectively.

Dosing has become a problemwith aluminum because of the diffi-culties of finding effective prepara-tions. But I think aluminum is still a reasonable choice. People usingaluminum binders have years ofexposure with no effective means ofeliminating the aluminum. I’m notsure we have those same concernsin dogs and cats.

Fernandez del Palacio: Calciumcarbonate and calcium acetate are themost common calcium-containingbinders. They have replaced alu-minum-based salts in people in orderto avoid the toxicities secondary toaluminum. However, due to a lower

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phosphate-binding capacity thanaluminum, high doses of calciumcarbonate are required to reduce theserum phosphate concentration toacceptable levels. Calcium acetateachieves similar control of the serumphosphate concentration as calciumcarbonate at a lower dose of elemen-tal calcium. The main disadvantageof calcium salts reported in people isthe associated hypercalcemia andmetastatic calcification.

Elliott: There are no published cli-nical studies comparing the availablephosphate binders (calcium contain-ing or noncalcium-containing) inveterinary medicine. Anecdotallyand by extrapolation from humanmedicine, one would recommendclose monitoring of serum calciumconcentrations when using calcium-containing phosphate binders be-cause the risk of hypercalcaemiamay be higher than with noncalcium-containing phosphate binders.

Do we know if adding a phos-phate binder to a maintenance dietcontaining a standard amount ofphosphate has a chance of success? Ihave always thought that you need toreduce the dietary phosphate intake,and if you can’t get animals to eat aphosphate-restricted diet, addingphosphate binders to their standardfood is unlikely to be successful.

Brown: In our laboratory study incats with early IRIS stage II chronickidney disease, we fed a mainte-nance diet with standard phosphatelevels but used a phosphate binder(Epakitin—Vetoquinol). It diddecrease the serum phosphate con-centration; initially, mean serumphosphate concentrations wereabove 5 mg/dl (1.61 mmol/l). Withthe phosphate binder, mean serumphosphate concentrations fell to 4.4mg/dl (1.42 mmol/l) (Brown SA,Department of Small Animal Medi-

cine and Surgery, College of Veteri-nary Medicine, University of Geor-gia, Athens, Ga: Unpublished data,2005). This may appear to be asmall effect, but it did move catswith chronic kidney disease to with-in our target range and was statisti-cally significant. I am not sayingthat this is the right approach, butyou can see an effect of binders.

Grauer: So this was about a 15% to 20% reduction in the serum phos-phate concentration with a mainte-nance diet.

Brown: That might be a fall-backplan if animals won’t accept a renaldiet. But it is likely that an intestinalphosphate binder will be more effica-cious with a renal diet than with amaintenance diet.

Lefebvre: One issue with phosphatebinders is that they may interact withoral absorption of other drugs thatare given to renal patients. If thephosphate binder is mixed with foodand the other drug is given at thetime of the meal, the absorption ofthe drug may be decreased.

Polzin: How serious would it be ifwe mix the binder in the food andthe animal grazes like many cats andsome dogs do? Is this a huge issue?

Grauer: One option would be to sim-ply withhold food for two hours afterthe other medication is administered.

____________________________Monitoring and rechecking

phosphate levels____________________________

Elliott: We now need to make spe-cific recommendations on managinghyperphosphatemia in terms of astaged approach and frequency ofmonitoring.

Fernandez del Palacio: We oftentreat dogs with chronic kidneydisease secondary to leishmaniasis,which is the main cause of chronickidney disease in our hospital.Hyperphosphatemia in those dogs ismainly present in advanced stages ofkidney disease. Some of these dogshave very high phosphate levels (18mg/dl or 5.81 mmol/l) at diagnosis.In our experience, a standard treat-ment based on stabilization of thepatient (e.g., fluids, antiemetics, H2receptor blockers), ACE inhibitors,calcium channel blockers (if hyper-tensive), allopurinol (for leishmania-sis), and a phosphate-restricted renaldiet helps maintain a serum phos-phate concentration of less than 6mg/dl (1.94 mmol/l) in most dogs.However, when diet is not wellaccepted by a dog or phosphatelevels remain higher than normal amonth later, we introduce an intes-tinal phosphate binder.

Gerber: In Switzerland, we try toreduce serum phosphate concentra-tions by feeding a renal diet first.Usually we do not achieve totalcontrol of phosphate, so we add analuminum-based phosphate binder,which is still available in Switzerland.

Brown: Another concern we shouldaddress is the frequency of rechecksfor assessing phosphate balance inpatients with chronic kidney disease.

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When diet is notwell accepted orphosphate levels

remain high, we introduce a

phosphate binder.—Dr. Fernandez del Palacio

Elliott: Once you have introducedthe treatment—a change in diet,phosphate binders, or both—andyou recheck the patient in four tosix weeks to ensure compliance,then monitoring every two to threemonths is frequent enough for IRISstage II to III.

Brown: So ask them to return in onemonth and then check them everytwo months?

Polzin: Our philosophy is morefrequent rechecks in the early stages.Then you can back off depending onhow the patient responds. For dogsand cats in IRIS stage III, you canrecheck them every three or fourmonths. And you can recheck catsless often if they are stable. Dogsand cats in stage IV may requiremore frequent visits.

Grauer: We should not lose sight ofthe fact that checking early allows usto look at other parameters beyondthe serum phosphate concentration:blood pressure, proteinuria, urinecultures, and possibly imaging stud-ies. This allows us to have a betterhandle on the stability—or lackthereof—of the disease process.

Polzin: If you wait too longbetween examinations, compliancewill fall precipitously. I think threeto four months is the longest youcan go without having to reintro-duce any drug in this situation—including phosphate binders—to clients.

Grauer: It depends, too, on whetherthere are other medications onboard. If you have a hypertensive,proteinuric patient on ACE inhibi-tors, you’ll need to look sooner atresponse, and you may or may notinclude your serum phosphate evalu-ation at that time.

Polzin: Again, there is a chance youwon’t see much change in the phos-phate level if you evaluate it too soon.

van Dongen: You only start evalu-ating the phosphate level once otherparameters have stabilized, such asproteinuria.

Polzin: As mentioned earlier, itdoesn’t have to be solved in the firsttwo weeks of treatment.

van Dongen: You have a reason for regular checkups in the begin-ning. But don’t monitor phosphatelevels only; also follow up on clinicalsigns, the intake of fluids and food(e.g., quantity, quality, amount ofrenal diet), parameters indicative ofrenal function itself (e.g., plasma cre-atinine, proteinuria, improvement inurine sediment), and underlying orsecondary abnormalities, such ashypertension. It does become impor-tant to reevaluate phosphate after thepatient has stabilized.

Brown: I used to recommend moni-toring at two-week intervals, but Inow realize that’s too frequent toreassess the full effects of either diet or a binder on serum phosphateconcentration. If you put an animalon a diet, recheck it in one or twoweeks, add a binder, and then recheckit in another week or two, soon youmay be overdosing the binder andinterfering with food intake. So a pre-ferred plan would be to recheck oncea month for the first three months.With this approach, once your patientis stable and eating a recommendeddiet, you then assess the serum phos-phate concentration a month later andmake a decision about a binder. Thena month after that, decide aboutadjusting the binder dose.

Grauer: So that raises this question:Should we recommend giving differ-

ent initial starting dosages of bindersduring different stages of chronickidney disease?

Polzin: If you start an IRIS stage IIanimal at the same dose that youstart a stage IV animal and your planis to recheck monthly for threemonths and then every three to fourmonths, the stage IV animal may notbe there by the third month.

Grauer: What would you recom-mend?

Polzin: We need to determinedifferent starting doses. There issome logic to reducing the serumphosphate concentration in parallelto the reduction in GFR. So de-termine the serum phosphate con-centration, figure out the bindingcapacity, get an idea of the dietaryphosphate intake, and calculate theappropriate dose to reduce theserum phosphate concentrationproportionately. It will vary, depend-ing on the diet and the severity ofthe GFR reduction.

Elliott: So the important point weneed to make is that phosphate bind-ing is a long-term treatment.

Polzin: And the dose is to effect.

Elliott: It’s also important toestablish the stability of the givendisease before starting the interven-tion. Because it is a long-termtreatment, the follow-up and moni-toring can be as infrequent as oncemonthly to begin with and then everytwo months, depending on the stageof disease.

Grauer: Would we automaticallyadd a binder to the diet as an initialtreatment for an advanced IRIS stageIII or IV patient, or would youalways assess the effect of diet first?

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Polzin: I don’t think hyperphos-phatemia is something you have tofix immediately, so I would startwith diet to see what that does. I’dfollow the diet until phosphate levelsare stable, which could be twomonths or more. At that point, youcould choose to intervene.

Elliott: In one feline study, research-ers rechecked the cats at four toseven weeks after a renal diet wasintroduced and then at four to fivemonths.9 There was very little changebetween the initial decrease in serumphosphate concentration after amonth or two on the diet. These werecats in IRIS stages II and III. Four-teen cats were fed the renal dietalone or renal diet and aluminiumhydroxide, and eight cats were fed a standard maintenance diet.

Brown: And this study was on dietalone?

Elliott: Primarily. Some of these catswould have been reassessed at pointsin between, and two were then givenphosphate binders because researcherswere not happy with the degree ofphosphate restriction. I think only twocats out of 14 in the first four to fivemonths needed phosphate binders.These cats tended to be in more ad-vanced stages of kidney disease, sothe diet alone was insufficient tocontrol the serum phosphate concen-tration and PTH. Thus, the degree ofphosphate restriction needs to be tai-lored to the individual cat. A logicalway to do this is to regularly reassessthe treatment response in relation toa defined posttreatment serum phos-phate target concentration; practition-ers should use stepwise increments ofphosphate restriction each month untilthey achieve effective control.

Cowgill: Particularly as you treatthese late IRIS stage III to stage IV

animals, it is problematic to throwall of the therapy at the patient atonce. It is more tolerable for the ani-mal and the client in steps, and theyare not dealing with four or fivemedications at the beginning.

Grauer: I don’t disagree with that.But in my experience, in an ad-vanced IRIS stage III or stage IVpatient, it’s unlikely that diet alone isgoing to get you where you want to

be. So you’re right; there are differ-ent ways to approach it. These catsor dogs are fragile; therefore, youshould change the diet gradually. Ifyou have a phosphate binder thatdoesn’t affect palatability, this mightnot be a bad time to introduce it soyou aren’t introducing a subsequentchange down the road.

Polzin: Do you think stepwise ther-apy is a problem in terms of serumphosphate concentration adjustment?

Grauer: No.

Cowgill: What is a dog’s life expec-tancy in IRIS stage III or early stageIV? Six or eight months?

Polzin: We didn’t look at the data inthose terms, but that’s probably right.

Cowgill: So are you going to taketwo and a half months to get this ani-mal on a low-phosphate diet?

Elliott: Should we check dogs thatare in the late stages after four weeksand add the phosphate binder then?

Cowgill: You may want to be moreaggressive with your approach. Idon’t have evidence, but my feelingwould be that hyperphosphatemiamay accelerate their demise.

Elliott: Could we say that with acertain level of hyperphosphatemiayou should treat initially with dietand binders? What if the serumphosphate concentration is higherthan 6 or 6.5 mg/dl (1.94 or 2.10mmol/l) after one month?

Cowgill: Then you have two op-tions. You could either try to get agreater proportion of dietary phos-phate reduction or add a binder.

Polzin: You could set two targets: 6 mg/dl (1.94 mmol/l) at one month,and 4.5 mg/dl (1.45 mmol/l) at twomonths. If you are above 6 mg/dl(1.94 mmol/l) at one month, thenyou add the binder. If you are below6 mg/dl, then you keep going.

Brown: So you are proposing thatat one month, if the animal’s serumphosphate concentration is above 6mg/dl (1.94 mmol/l), you would adda binder, bring that animal back in amonth, and continue at monthlyintervals until you reach stability inthe serum phosphate concentration?Ultimately do we still have the sametargets that we had before?

Polzin: Yes. The serum phosphateconcentration target stays the same.

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In my experience,in an advanced

stage III or stage IVpatient, it’s unlikely

that diet alone is going to get you where you

want to be.—Dr. Grauer

Ideally, you would reach it by twomonths. If you don’t, you might con-sider increasing the binder dose.

Brown: In all likelihood, the IRISstage IV animal would be on a phos-phate binder at one month.

____________________________Calcium monitoring____________________________

Brown: Practitioners should alsomonitor calcium.

Elliott: What limits are we puttingon calcium? What should we do ifwe are outside of those limits?

Polzin: A lot of these dogs and catsare hypercalcemic, but this isn’t neces-sarily associated with ionized calciumelevations. Frankly, I am not 100%sure what hypercalcemia means phys-iologically or pathologically to a pa-tient. It might suggest a higher proba-bility of tissue mineral deposition.

Grauer: You have made a criticalpoint. If you see hypercalcemia, youneed to analyze ionized calcium levels.

Polzin: But is it going to changewhat you do? Clearly it will if theionized calcium is elevated, but if it’snot, what do you do?

Brown: If the animal is hypercal-cemic, you should measure the ion-ized calcium. If the ionized calciumis in the normal range, you make noadjustments; you just monitor thecalcium. But if the ionized calcium is elevated and the animal is taking acalcium-containing phosphate binder,I would switch to a noncalcium-containing binder.

van Dongen: If you use a calcium-based binder, it would be wise tomonitor the calcium and preferablyionized calcium levels.

____________________________Conclusion____________________________

Elliott: Our recommendations forserum phosphate concentrationmanagement are summarized onpages 8 to 9. This treatment is forstable chronic kidney disease pa-tients, and the benefit comes fromlong-term control of the serum phos-phate concentration. Manage yourkey problems first before consideringthe serum phosphate concentration;

for example, address pyelonephritisand severe hypertension. Demon-strate stability in the patient withchronic kidney disease by perform-ing serial serum creatinine measure-ments every two to four weeks.Phosphate restriction can also beaddressed at this time.

Control of the serum phosphateconcentration should be achieved bygradually introducing a phosphate-restricted diet. All commercially avail-able renal diets can be used to achievephosphate restriction. They should beintroduced gradually over a period ofseven days. The greater the proportionof the renal diet fed, the better.

Patients should be reevaluated

after four weeks. If the serumphosphate concentration is greaterthan 6 mg/dl (1.94 mmol/l) at thistime, introduce intestinal phosphatebinding agents, reevaluate afteranother four weeks, and adjust thedose to achieve the target level forthe stage of chronic kidney disease.If the serum phosphate concentrationis less than or equal to 6 mg/dl (1.94mmol/l) after four weeks, continuedietary therapy for an additional fourweeks. If the target serum phosphateconcentration has not been achievedat this time, introduce intestinalphosphate binders.

____________________________References____________________________

1. Jacob F, Polzin DJ, Osborne CA, et al.Clinical evaluation of dietary modification fortreatment of spontaneous chronic renal failure indogs. J Am Vet Med Assoc 2002;220:1163-1170.

2. Elliott J, Rawlings JM, Markwell PJ, et al.Survival of cats with naturally occurring chronicrenal failure: Effect of dietary management. JSmall Anim Pract 2000;41:235-242.

3. Ross LA, Finco DR, Crowell, WA. Effect ofdietary phosphate restriction on the kidneys ofcats with reduced renal mass. Am J Vet Res1982;43:1023-1026.

4. Brown SA, Crowell WA, Barsanti JA, et al.Beneficial effects of dietary mineral restriction indogs with marked reduction of functional renalmass. J Am Soc Nephrol 1991;1:1169-1179.

5. Slatopolsky E, Bricker NS. The role ofphosphorus restriction in the prevention ofsecondary hyperparathyroidism in chronic renaldisease. Kidney Int 1973;4:141-145.

6. Slatopolsky E, Caglar S, Gradowska L,et al. On the prevention of secondary hyper-parathyroidism in experimental chronic renaldisease using “proportional reduction” of dietaryphosphorus intake. Kidney Int 1972;2:147-151.

7. Ross S, Osborne CA, Polzin DJ, et al.Clinical evaluation of effects of dietary modifica-tion in cats with spontaneous chronic renalfailure. J Vet Intern Med 2005;19:433A.

8. KDOQI clinical practice guidelines forbone metabolism and disease in chronic kidneydisease. Am J Kidney Dis 2003;42(suppl 3):S1-S201.

9. Barber PJ, Rawlings JM, Markwell PJ,et al. Effect of dietary phosphate restriction onrenal secondary hyperparathyroidism in the cat.J Small Anim Pract 1999;40:62-70.

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© 2006 Vétoquinol. All rights reserved. Cover art by Sandy Ostroff.

If you use a calcium-based

binder, it would be wise to monitor the calcium and

preferably ionizedcalcium levels.

—Dr. van Dongen

in the treatment of chronic kidney...

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