Fanconi Disease Management
Protocol for Veterinarians
by Steve Gonto

Dr. Steven Gonto
209 Hammocks View
Savannah Georgia, 31410
e-mail: Outdoc@aol.com

Definition: FANCONI DISEASE is a mammalian renal tubular reabsorption failure, usually genetic in origin, resulting in polyuria/polydipsia (PU/PD) with glucosuria; generalized aminoaciduria; proteinuria; loss of multiple vitamins, minerals, electrolytes and bicarbonate. These losses result in metabolic acidosis, protein-loss muscle wasting, weight loss, and myalgia. Left uncorrected, it causes increasing acidosis, while stressing the respiratory compensation system to its maximum effort, and leads to the progressive and degenerative renal and then multisystem failure, resulting in death. With early intervention and lifelong management, prognosis appears excellent for long term, healthy survival. Correction of the acid/base component appears to slow or in some cases, arrest, further degenerative progression. This disorder is prevalent in the Basenji breed of dog, although it appears that it can be genetically inherited or induced in all mammals.

Diagnosis: Often presents as polyuria/polydipsia or UTI. Positive diagnosis is made by glucosuria with normal or low blood glucose. All Basenjis should be tested by their owners monthly for urine glucose, ketone or protein loss using Gluco-Ketostix, Ames Combistix, Glucose/ Ketone Chemstrips or any similar test strips or tape, available from the diabetic testing section of pharmacies. Any positive reading should be reported to their veterinarian. Prevalence of Fanconi is high in Basenjis. Other breeds have been reported with similar clinical symptoms including Cocker Spaniels and Malamutes, all of which seem to benefit from identical medical management to Basenjis. Most common misdiagnosis is diabetes, or Cushing syndrome.

Onset: Age of first symptoms (PU/PD) is usually 5 to 7 years; however, it has been diagnosed from 3 to 11 years. Early diagnosis is essential. The earlier treatment is begun, the less renal damage exists, and thus fewer replacements are needed.

 

Labotatory tests to run

Initial Diagnosis and Quantification of Fanconi-induced losses: Once a working diagnosis of Fanconi disease has been made on the basis of a POSITIVE urine glucose in the absence of elevated blood glucose (and without predisposing events, such as poisoning), then the following tests should be run:

  1. Serum multi-chemistry panel, especially sodium, potassium, calcium, and phosphorous (looking for deficiencies).

  2. Venous Blood Gas Panel (looking for acidosis, low PaCO2, low bicarbonate level and low Base excess). These labs can usually be run by a human hospital, or new, inexpensive monitors like the I-Stat, and are ESSENTIAL (total CO2 on a chemistry panel does not suffice). Further specifics of blood gas analysis follow later in this protocol. Be aware that when the dog is in respiratory compensation mode, the CO2 level can drop very low, without visually evident hyperventilation or tachypnea. This is why the CO2 on a blood gas panel is often such a vital tool to assess the severity of the disorder. In very "late" cases, the respiratory compensation mechanism will have failed and the CO2 will be trending up to normal, while the pH is dropping precipitously, thus sending the dog into a potentially fatal acidosis crisis. Aggressive management in these "late" diagnosed cases may still be life saving.

  3. Thyroid Screening. A fair percentage of Fanconi afflicted dogs have been shown to be hypothyroid. Even if the thyroid screen shows hypothyroid, and replacement therapy is instituted, you should recheck the level in six months, after a Fanconi treatment regimen is begun. This way you can be sure that the thyroid deficiency was not due to out-of-control systemic acidosis and the resultant alteration of normal organ system function. If the thyroid screen is only mildly hypothyroid, you might even wait until the Fanconi regimen is stable and then recheck the thyroid function, prior to instituting thyroid replacement therapy. There have been cases where the repeat thyroid screen, in the Fanconi "corrected" dog, was normal.

  4. Urine Screening. Afflicted dogs will ALWAYS have dilute and alkalotic urine, from the high volume of ingested water and the bicarbonate loss. Likewise they will always remain glucosuric. What we want to check for on EACH follow up visit, is the presence of any possible UTI, since the sugar and pH situation in the bladder and kidney is a perfect set up for infection.

Follow-up laboratory suggestions:
Years of experience have shown that a good level of success can be achieved by following these basic guidelines for Fanconi-related lab studies:

  1. INITIAL BLOOD GAS and CHEMISTRIES as above noted.

  2. Follow up, usually eight to ten weeks after beginning full management regimen. This allows time for compensation mechanisms to slow down or stop, thus giving accurate long-term lab values.

  3. Repeat follow up, with all labs at 6 months after first follow up.

  4. Annual checkups and labs if all is going well.

  5. In repeat labs, try to make sure that the time interval between bicarbonate and vitamin dosing and blood being drawn is consistent with each recheck. Eight to ten hours following the last supplement dosing is an ideal time to draw blood for labs. If bloodwork is to be done in the AM, then no morning pills should be given; likewise, afternoon blood draws should be done late enough to avoid the peak absorption period. We want to try and get a set of labwork that approximates where the dog is existing most of the time, between pill doses. With the repeat labs, the goal is to adjust the initial doses up or down to try and obtain as NORMAL a blood chemistry and blood gas profile as possible. Most dogs, once controlled, are stable and healthy enough to follow this schedule for lab and doctor visits. MORE frequent follow ups or labs are NEVER an objection, if they are justified by the veterinarian's clinical intuition or if the dog is, in any way, showing less then extreme good health and optimal control of their disease. Also, any acute illness, pending surgery, additional thirst and urination (volume or frequency) as well as other unusual stress, symptoms or change in behavior or appearance is ample justification for repeating labwork.

Therapeutic Goals:
 Restoration of normal blood chemistry by matching losses of bicarbonate, protein and vitamins/minerals.

  1. Bicarbonate is dosed, using blood gas analysis, to match the Fanconi induced losses and return blood to normal acid/base balance without depending on body's short-term compensatory mechanisms. Success will be seen as an increasing PaCO2 (as the respiratory compensation mechanism, which demand metabolic work, turns off).

  2. Create a positive protein balance allowing return to tissue building and to support muscle mass and strength. This is accomplished with a HIGH protein diet, since ordinarily this is NOT "renal failure." In cases compounded with renal failure, such as other acute diseases or chronic changes of old age, see modification of the protocol mentioned later, under "Renal Failure "Hybrid" Protocol."

  3. Normalize Electrolytes. Support the body's vitamin/mineral needs, including trace minerals. Note: Correction of bicarbonate loss and correction of blood chemistry seems to slow progression of this disease to the point that it is inconsequential in a dog's life span. Serial GFR and creatinine clearances in some research test dogs have confirmed this, although these tests are too expensive and invasive to recommend routinely. Acute one time dialysis is rarely needed, but has been used successfully as a lifesaving measure when late diagnosis has resulted in acute renal failure. Kidney function has returned to post-dialysis in some of these cases.

Managment dosing guidelines:

Note that these are recommendations only, based on over ten years' and many hundreds of dog's experience. NO general guideline can take into account all the variables that any individual condition may present, thus we ask that ALL veterinarians use their individual clinical training and judgement in prescribing and designing any treatment regimen for an afflicted dog.
This protocol is designed only as a tool to assist the veterinarian and should NEVER be used without the care and expert advice of a veterinarian in treating any dog.

INITIAL MINIMUM TREATMENT FOR POSITIVELY DIAGNOSED DOG: INDIVIDUAL DOG'S LOSSES WILL BE CORRECTED BY TITRATING UP FROM HERE. Please note that all dosages are based on the average 22-27 lb. (10-12.5 kg) Basenji. Please calculate doses up or down for treating other size dogs or animals afflicted with Fanconi.

  1. Fresh water freely available. Do not add any medication or supplements to regular water or food items as this may cause a dog to stop eating their regular meals.

  2. Any good quality dry food may be fed, with the addition of at least one can per week of HIGH PROTEIN "wet meat" mammal meat based dog food (beef, lamb, etc.) to replace long-chain amino acids and phosphorus. Poultry based foods have proven far less effective in management of this disorder then mammal based meats. The only exception to this high protein diet, in this protein-losing uropathy, is documented renal failure (increasing BUN/CREATININE). In this type situation, see the "RENAL FAILURE HYBRID PROTOCOL" section later in this instruction set.

  3. PET-TAB PLUS-type vitamin/MINERAL supplement tablet. ONE tablet, divided 1/2 tab BID for asymptomatic dogs diagnosed ONLY by positive glucosuria, TWO tabs daily, given ONE TAB BID for symptomatic dogs. TITRATE HIGHER for dogs with MINOR hypokalemia or hypocalcemia.

  4. PET-CAL-type vitamin D-phosphorus replacement tablet. Given 1/2 tab BID in asymptomatic dogs. ONE tab BID in symptomatic dogs. Phosphorus loss is a hallmark of Fanconi disease and since it is sequestered from muscle mass into the blood, standard chemistry panels may not reveal the full extent of the loss. If Fanconi afflicted dogs show a loss of muscle mass and any sign of MYALGIA after they appear corrected on BLOOD GAS and CHEMISTRY panels, increasing the PET-CAL dose, as well as CENTRUM and AMINO FUEL listed below, is a good idea.

  5. CENTRUM VITAMIN-type COMPLETE vitamin/mineral tablet (high potency), at a dose of ONE tab/week in dogs with PU/PD (no dose needed in fully asymptomatic dogs). This covers the loss of many TRACE elements caused by the high water washout of the PU/PD. In cases of "unusual symptoms" in a corrected dog, such as seizures, acute onset blindness or other problems without clear cause, it does not hurt to empirically TITRATE UP the CENTRUM to as high as one tab EVERY OTHER DAY, since we have seen multiple "strange" symptoms resolve this way. These symptoms may have well been caused by trace elemental losses and deficiencies in these dogs.

  6. AMINO FUEL-type COMPLETE amino acid preparation. (Tablets and granulated powder are available in body building section of General Nutrition Center or other similar store). Dose at one tab/week (or equivalent powder) if asymptomatic. Titrate up as high as one tab (or equivalent powder), every-other-day, in cases of extreme muscle wasting, poor coat or unresolved skin problems. In cases where a HYBRID renal failure/Fanconi regimen is being used, the Amino Fuel dose goes as high as 1/2 tab (or equivalent powder) BID (when given with LOW protein foods to correct increased BUN and CREATININE)

  7. SODIUM BICARBONATE ANTACID TABLETS. This is THE MOST IMPORTANT component of this protocol. Without correction of the Fanconi bicarbonate loss and correction of serum acid/base imbalance, this disease remains fatal. Sodium Bicarbonate 10-grain antacid tablets (similar in size and appearance to an aspirin tablet) are available OTC from any major pharmacy. It is very inexpensive and thus most economical to purchase in a 1000 count bottle form. (Current 1999 pricing varies from $7 to $30 per 1000 tablets). I do not recommend using powdered bicarbonate (baking soda), since the volume of dosing would be very difficult and the level of medical purity (compared to the tablets) is questionable. Bicarbonate will be dosed based upon a VENOUS BLOOD GAS PANEL. Emergency dosing can be done at a rate of THREE 10 grain tablets BID, but this is VERY undesirable compared to a measured correction. BICARBONATE TABLETS MUST BE GIVEN INTACT. Pills can be hidden in a small amount of food, such as VELVEETA cheese ball or baby food ball or hidden in a bit of meat, etc. Since we are giving multiple tablets BID, and wish to maximize owner compliance and dog cooperation, I recommend hiding pills in food treats for easy and atraumatic administration. Some owners still prefer to just "pill" their dogs, and this is okay if done very gently. "Treat-time"... with LOTS of excitement, seems to make the twice a day pill giving time a lot easier on owner and dog. In cases where the dogs are resistant to taking the bicarbonate, it can be crushed up (the least amount possible) and then placed inside hollow gelatin capsules (available at pharmacies and health food shops). These capsules can then be hidden (without as easy detection by the dog) in a little treat for administration. Also, it has been reported that some dogs get "gassy" or flatulent with the bicarbonate, but this passes in a few weeks. Meanwhile, some dogs tolerate the bicarbonate best at meal time (less apparent GI distress). Other dogs do much better when the bicarbonate is spaced away from their meal time by an hour or two, so that the normal stomach acids are not neutralized while in the presence of food, which can result in vomiting and poor food tolerance. This finding will vary from dog to dog, so trial and error is the best way to optimize the pill and food relationship.

  8. POTASSIUM SUPPLEMENTATION such as TUMIL-K or UROCIT-K is used in about 5% of Fanconi dogs for persistent hypokalemia, even once otherwise "corrected." These tablets are dosed by blood chemistry and dogs taking them should be followed a bit more frequently. These tablets must also be given intact, especially UROCIT-K, which is a "timed release matrix" delivery vehicle. Crushing some potassium tablets can result in catastrophic overdosage for the dog.

    POTASSIUM DOSE RECOMMENDATION SCALE: Note that UROCIT-K is 5 MEQ per Tablet and TUMIL-K is 2 MEQ per tablet.

    Potassium Measure in Blood Recommended Starting Dose of Potassium
    1.50 to 2.00 MEQ/L 15 MEQ (1620 mg) P.O. B.I.D.
    2.10 to 2.75 MEQ/L 10 MEQ (1080 mg) P.O. B.I.D.
    2.76 to 3.75 MEQ/L 5 MEQ (540 mg) P.O. B.I.D.


    As with any administration of potassium, repeat lab work should be followed closely until stable (one lab per week for four weeks, and as symptoms dictate). Thereafter, routine follow-up should suffice, but bloodwork should be done at six month, rather then one year intervals. No cases of hyperkalemia have been encountered to date and dose must be as high as needed to correct deficiency, but titrate up very carefully.

Acute emergency management:

Acute one time dialysis is rarely needed, but has been used successfully as a lifesaving measure when late diagnosis has resulted in acute renal failure. Kidney function has returned to pre-dialysis levels in some of these cases. Calculating volumes for fluid dialysis must account for these dogs' already high fluid intake and losses. 4X base fluid levels have been used successfully by some veterinarians. Adding I.V. bicarbonate to slowly correct pH. and I.V. nutritional support "if available" may help with life support and recovery. Oral alimentation once eating (Sustical, Nutrical, or Ensure) should be used till the dog is weaned off IV to regular diet.

Renal failure "Hybrid"-Protokol:

As more dogs have survived long term on this protocol, we have seen multiple cases of renal failure onset from various causes, most often just the "normal" slow onset renal failure of aging. In these cases we have HYBRIDIZED the Fanconi Protocol to allow for the maintenance of acid/base chemistry, while correcting the problems of the renal deficiency. We start with life saving measures as needed, including fluid, peritoneal or serum dialysis as needed. We then institute a diet as follows:

  1. LOW protein dry or "canned" food. Fresh water remains freely available.

  2. Add in up to 1/2 tablet of the AMINO FUEL or other amino acid preparation daily, to cover our protein loss.

  3. Increase CENTRUM type multivitamin to QOD.

  4. Drop the PET-CAL type tablet from the regiment, since in renal failure serum PHOSPHORUS tends to go UP.

  5. Labwork and physical exams should be performed MORE frequently in renal insufficient dogs.

Acid-Base-Balance:
The importance of correcting the acidic blood pH created by the loss of the bicarbonate ion in this disorder cannot be overemphasized. Acidosis is the prime contributor to the progression of this disorder and it seems to be the stabilizing hallmark of this protocol's success. A Venous Blood Gas is the ONLY means of establishing the pH and bicarbonate need. An arterial blood gas in more difficult to obtain and unnecessary. A "total carbon dioxide" or bicarbonate level as reported on a regular multi-chemistry panel DOES NOT approximate the pH in this situation, nor let you calculate it, due to continued blood metabolization. Unless you have access to a blood gas analyzer, you must enroll the assistance of a human hospital, or major veterinary center, in the running of a Venous Blood Gas (VBG). Every respiratory therapy department, intensive care and neonatal unit has a blood gas analyzer. It is totally automated and costs under ten dollars per test in chemical reagents; therefore, the charge made to vets has been minimal. Please explain to the lab director that it is a genetic, noncontagious, disorder and a heparinized sample of dog blood is identical to human blood with respect to the analyzer. Without a blood gas to compare pCO2, pH, and buffer levels, this disease is virtually impossible to manage. While treating Fanconi patients, some private veterinary practices have now purchased the hand-held I-STAT type blood gas analyzers. These devices have become affordable enough for veterinarians nationwide to justify purchasing them to add to their in-house diagnostic laboratories. These analyzers have proven themselves valuable far beyond the treatment of Fanconi patients.

Technique for obtaining venous blood gas:
"Heparin wash" a 3cc syringe (draw up a drop of heparin, draw the barrel in and out and then squirt out the heparin). Using this syringe, draw a 2.5cc sample of venous blood. Express out any air from syringe and roll syringe in hand to mix residual heparin and blood. Recap the syringe tightly and place it into a sealable Ziploc-type plastic bag. Immediately immerse the "bagged" syringe in a cup of ice water. The ice and water together should make total contact around the syringe barrel, to keep the blood within uniformly cold. While a human blood gas sample on ice is good for approximately one hour, the Basenji blood seems to metabolize oxygen and produce carbon dioxide at a higher rate, therefore, the sample must go from dog to machine in 30 minutes or less to get a truly accurate reading. Fifteen minutes from dog to blood gas machine is ideal. The values obtained will be pH (acid/base level), pCO2 (carbon dioxide level), and B.E. (base excess; a measure of the bicarbonate buffering level). Any other levels, which their machine produces, should be noted. These may include: HCO3 (calculated by the Henderson-Hasselbach equation, is also a measure of buffering level), Sat. (hemoglobin oxygen saturation), or other values.

Helpful hints in several areas:

MEDICAL MANAGEMENT: Periodic follow-up for UTI is essential since there is always a glucosuria present. Antibiotics appear to be tolerated normally. While symptoms such as PU/PD should be watched, these dogs have tolerated short-term steroids, via I.M., I.V., and P.O. routes for neurologic and orthopedic problems. Chronic but periodic low dose steroid use for treating flea induced skin problems has also appeared to be benign. Chemotherapeutic agents have been used on some Fanconi dogs for treatment of different tumors. Their reactions were not observed to be different than the non-Fanconi canine population, although the less nephrotoxic agents have been the choice of the oncologist involved. Some dogs have been mildly incontinent even with correction of all measurable values. In these cases, Phenylpropanolamine (25 mg of the veterinary form PROPAGEST or regular strength 25 mg DEXATRIM DIET AID), given at a rate of ONE TABLET DAILY, one-hour before bed, has allowed owners and pets to sleep through the night and prevent bed-wetting. The Pheylpropanolamine is claimed to strengthen the bladder sphincter valve, which seems to be an asset in dogs like the Fanconi afflicted, where urine volume, glucose and pH all contribute to potential "urgency" or "leaky" incontinence. Please use this medication only with a fully corrected dog, since it only MASKS symptoms and I would prefer to correct any underlying problem first. Sudden change in urination habits and any incontinence in the Fanconi dog should first be considered as a urinary tract infection, until proven otherwise.

SURGICAL MANAGEMENT: General anesthetics have been well tolerated in this group, although a preanesthetic potassium measurement would not be unreasonable. Emergence time from general anesthesia, as well as the reversal of sedative hypnotics, appears slightly prolonged. I would strongly suggest that emergence from general anesthesia be accompanied by low amounts of supplemental oxygen, as any weakness or "hypoventilation induced hypoxia" in these already compromised dogs would present an unneeded stress on their renal status, as well as their overall physiology. In cases of prolonged NPO status or long surgery, several MEQ of HCO3 (I.V. form) added to a liter of IV fluid can help prevent intraoperative systemic acidosis.

GENERAL INFORMATION: Once controlled, the Fanconi dog should be treated as with any other dog. They are prone to any other disease process and are able to be treated as any other dog. Exercise should not be limited, (we have had long distance runners, mountain climbers and lure coursing champions who were well-managed Fanconi patients) although fresh water should always be available, and afflicted dogs should be offered water much more often then "usual" during such stress activities. Added ideas for treats in which to hide pills include, Velveeta Cheese Slices, which have a malleable, Play-Doh type consistency and can be "formed" into balls with pills inside. Large elbow macaroni cooked in beef or chicken soup or stock (this can be prepared in advance and refrigerated). A few noodles are given as a tease, which leads to the pill filled ones. Hiding the pills in tiny balls of beef baby food or cat food (more aromatic than dog food), hot dog slices, bratwurst and knockwurst have also been popular. Small quantities of everything from ice cream, cream cheese, peanut butter to bologna have been used successfully by various owners. Creativity in this area is vital, but remember, once you find a pill hiding technique that works, it is best to stick with that item as long as the dog will take it, since these are creatures of habit. Also, owners of multiple dogs can use competition and jealousy between dogs to get the pills easily taken, by making sure that the non-afflicted pets are given a NON-medicated treat while the Fanconi dog is given its pill-hiding treat. When another "competitor" for food is present, the pill-containing treat seems to get swallowed much faster and without much "investigation" by the afflicted dog.

FURTHER INFORMATION: Many wonderful sites are available on the INTERNET with suggestions on "pill hiding treats" and other topics pertaining to owning and feeding a Fanconi afflicted dog. Likewise, many local or regional Basenji breed club magazines have interesting owner articles on this subject. My motto is that information is always your best ally in fighting any disease, and a great place to start is with either the nationally circulated breed magazine or with some of the excellent regional and breed club newsletters. Likewise, "networking" with other Basenji owners via clubs and shows is a great asset to "staying in touch" with pertinent health news and breakthroughs.