Part I: The Kidney in Health and Disease

Prevention and treatment are not the same, and phosphorus may be more important than protein.

Martha S. Gearhart, DVM
Diplomate, American Board of Veterinary Practitioners

As a Senior Veterinary College student, I was assigned to the Intensive Care Unit and spent one very long afternoon watching an elderly dog on fluids die in uncontrollable seizures, because his owners refused to consider euthanasia for this poor animal in total kidney failure. Eleven years later, I euthanized my own dog for the same illness, and both of these experiences have given me a special interest in this disease. Interestingly, pet food manufacturers are also very interested in kidney failure (alternatively called renal failure), and the increased availability of low protein diets, marketed for their reputed benefits to an old dog's kidneys deserves some scrutiny. In truth, the role of protein, phosphorus, and even Vitamin D are all hotly debated by veterinary scientists researching kidney failure. Yet much of the marketing claims made today on the dog food shelf of your grocery store focus primarily on protein levels and may actually reflect the results of experiments done over a decade ago, often on rats rather than dogs, and are now frequently challenged by newer studies.

One thing every scientist and clinician do agree on, however, is the management of a patient actually ill with kidney failure. This pet must have phosphorus restricted if there is to be any hope of slowing the progressive, inexorable rate of kidney destruction. Additionally, if that pet is nauseous or has vomiting and diarrhea, then protein must also be restricted. In practical terms, most pets in renal failure are fed scientifically-formulated diets that reduce both nutrients and the benefits are usually quickly evident to both the pet's owner and the pet's doctor. But what of the aging dog? Or the dog with subtle changes in his urine, but not yet any changes in blood values? What diet should be fed here? Can we help such a dog now with dietary changes, or do we simply have to wait until illness actually occurs? And how common is kidney disease in the general population of older dogs? Can so-called "senior diets" be harmful? Particularly since some studies indicate kidney changes in up to 85% of the canine population over five years of age, and other studies suggest that kidney failure is the second leading cause of disease-related deaths in dogs, second only to cancer or heart disease?

Before we can answer such questions, we have to understand the kidney -- no small challenge since this complex organ is much more than an exquisite filter, cleansing the bloodstream of toxins and keeping the body's salts and minerals in balance. The kidney is also an endocrine organ -- a factory for hormones which variously stimulate red blood cell production by the bone marrow (erythropoietin), induce calcium absorption by the intestines (the activated form of Vitamin D -- calcitriol), and affect blood pressure throughout the body by retaining sodium (renin). These distinctly different roles interact in the failing kidney. Anemia from failed production of erythropoietin can increase the rate of kidney failure due to low oxygen in the blood. Low amounts of activated Vitamin D can hasten failure through calcium and phosphorus imbalances which lead to destructive mineral deposits in the kidney itself. Excessively high or low blood pressure will also damage the kidney. An animal in kidney failure eventually becomes far more complex than simply an individual being poisoned by its own body processes because the key filter has failed.

The Normal Kidney

The functioning unit of the kidney is the nephron, and clinical disease will not develop until roughly 2/3rds of the nephrons are damaged or destroyed. Such reserve (70% of kidney tissue) explains why persons and animals can donate an entire kidney and still live a normal lifespan. However, the remaining nephrons do change to meet the increased demands placed upon them. They must work harder and become more efficient if the same amount of blood is to be processed. The tiny, twisted capillary that sits in the glomerulus must expand to allow more blood to flow. Consequently, the glomerulus enlarges as well to receive the plasma-like, low-protein filtrate that passes out of the capillary. The various tubules and ducts that process that filtrate must also increase their efficiency -- whether it is to reabsorb sodium and bicarbonate (proximal convoluted tubules), excrete or absorb water (Loops of Henle), or balance potassium and acid exchange (distal convoluted tubules). Collecting ducts then carry the final product, urine, to the central portion of the kidney and down the ureter to the bladder. Within the kidney, the length of the nephron, including the collecting duct, approximates 45 - 65 mm (2 - 2.5 inches).

The three hormonal roles of the kidney take place primarily in the glomerulus and the proximal tubules where the process of filtrate transformation and urine production begins. This is logical, since the plasma filtrate at the beginning of the filtering process most closely reflects the conditions in the total body, allowing the hormonal responses of the kidney to quickly correct any imbalances detected. If oxygen tension is low as it is at high altitudes, erythropoietin will be released to stimulate the production of more red blood cells by the bone marrow. In the renal failure patient, injections of erythropoietin will reverse the anemia, increase oxygenation of the kidney, and often extend the life of the patient.

The second hormonal function of the kidney also involves blood flow. If blood pressure drops and flow to the glomerulus falls, such as occurs in shock after an automobile accident, then glomerular cells release the hormone renin which can increase blood pressure, consequently restoring blood flow to the kidney. Blood pressure is increased in several ways, but chiefly through salt retention by the kidney itself. In the failing kidney, blood pressure also decreases, so renin is released. The resulting hypertension initially increases blood flow though the weakening kidney, but, ultimately, this high blood pressure destroys the fine glomerular capillaries. Terminally, all the excess sodium in the body can lead to edema and heart failure, further complicating a severe condition.

The final hormonal system involving the kidney is thought by some researchers to be the most important to the renal failure patient. If calcium levels in the blood are too low, stores of Vitamin D will be converted to its active form and released as a hormone into the body to increase calcium absorption by the intestines. The importance of calcium to the body, and its role in kidney health and disease, cannot be explained without discussing phosphorus at the same time. These two minerals are the primary components of bone and bone-like deposits will form in normal tissue if either mineral is too highly concentrated in the bloodstream. This happens passively simply because calcium will precipitate as a phosphate salt if enough ionized calcium and ionized phosphate are in proximity to each other. To avoid this and maintain a safe and constant ratio between the two minerals, the body exercises several hormonal controls, both in the kidney, in the thyroid, and in the parathyroid gland.

Additionally, calcium is as essential to heart and muscle function as are sodium and potassium, because all of these minerals are exchanged back and forth across muscle cell membranes to effect contraction. Severe imbalances of any of these minerals create weakness and abnormal heart rhythms. The kidney/parathyroid gland hormonal feedback systems work to conserve calcium and to prevent the deposition of bone in soft tissue. Since calcium and phosphorus come into the bloodstream from both the diet and from bone, the kidney and the parathyroid glands exert their effects chiefly on the intestines and the skeleton as well as on the major route of mineral excretion -- the urine produced by the nephron tubules.

The activated form of Vitamin D produced in the kidney is considered a hormone because it exerts its actions on a distant location. Chiefly, it increases calcium concentrations by increasing absorption from the intestines. Parathormone, produced by the parathyroid gland in the neck, is also sensitive to the blood's calcium concentration. When calcium levels are low, parathormone encourages mobilization of calcium from bone. Since phosphorus is liberated from the bone at the same time, parathormone increases the excretion of phosphorus from the kidneys to keep the ratio between the two minerals constant.

In the early stages of kidney disease, these hormonal feed-back systems work well, but by the time the kidneys have only 15% to 25% of their remaining nephrons still functioning, then these control methods can actually contribute to disease. Decline and eventual death are very rapid from that point. Due to lack of activated Vitamin D combined with excessive parathormone levels, calcium phosphate salts actually precipitate in the kidney itself, hastening its destruction through mineralization. Blood pressure becomes dangerously high due to excessive release of renin -- the kidneys' attempt to increase blood flow faster and harder through fewer and fewer nephrons. This eventually destroys the delicate, remaining glomeruli and associated capillaries. Finally, erythropoietin cannot be produced, and the resulting anemia further decreases the blood supply to the kidney. An anemic renal failure patient is often considered to be terminal ("end-stage"), because erythropoietin production is one of the last things to fail.

Diseases Affecting the Kidney

Given the complexity of the kidney, it is not surprising that many breeds report kidney disease in young dogs due to gross malformations, subtle abnormalities in development, or premature atrophy of nephrons. Kidney disease can occur sporadically in any young dog, but distinct syndromes have been defined for the cocker spaniel, Norwegian Elkhound, Lhasa apso and Shih tzu, Basenji, Samoyed, Doberman pinscher, Cairn terrier, Standard Poodle, Pembroke Welsh Corgi, soft-coated Wheaten terrier, and Bull terrier. In some, the genetics have been precisely defined, while, in others, a higher-than-expected breed incidence of kidney disease is all that has been reported to date. Tiny puppies may be presented for stunted growth, poor appetite, vomiting, diarrhea, uncontrollable house training, and drinking lots of water. Alternatively, dogs as old as five years of age may begin to show these signs of illness. Since the nephron is such a complicated piece of plumbing, any single part of it can fail to develop properly and lead to disease in a young dog.

A few well-described cases illustrate this. The Samoyed type of congenital kidney disease is an abnormal multiplication of cells in the glomerulus, eventually choking this structure. It is inherited as a dominant, sex-linked trait, killing males before fifteen months of age while carrier females may live a normal lifespan despite abnormal urine and bloodtests. In contrast, Cairn terrier pups are usually recognized as stunted and unhealthy well before weaning (four to six weeks of age), because huge cysts form not only in the kidney, but in the liver as well, actually swelling the abdomen. These cysts are believed to originate from the external capsule of the kidney and liver. In the kidney, the nephrons themselves are normal, but they are progressively destroyed by pressure from the cysts. In contrast, the Basenji is an animal model for human Fanconi syndrome since loss of function is so specific to tubular disease. The dog suffers from Fanconi-type mineral imbalances and loss of glucose before the later signs of renal failure such as vomiting, diarrhea, and dehydration appear. Finally, affected Lhasa apso and Shih tzu puppies will have mishapened kidneys with additional microscopic abnormalities. The kidneys may be dumbbell in shape, with normal tissue absent from the middle of the kidneys. Under the microscope, nephrons may be small, irregular, and not fully developed, looking more like the immature nephrons present in the kidney of the fetus.

Beyond genetics and birth defects, poisons and infections can injure any or all parts of the nephron. Ethylene glycol (antifreeze) destroys the kidney only after it has been metabolized to oxalic acid in the liver. In that form, it precipitates as calcium oxalate crystals in the tubules, effectively blocking and destroying them. Infectious bacteria can also attack the nephron, invading through either the bloodstream and into the glomerular capillary tuft, or directly from the urine itself, migrating up from the bladder, through the tubules and deep into the kidney. Bloodclots can effectively destroy kidney tissue as well. Finally, the glomerulus may even filter circulating antigens and antibodies, depositing these non-infectious but still reactive complexes in the glomerulus, leading to its destruction.

Regardless of the specific location or cause of kidney damage, once 60 - 75 % of the kidney is destroyed, abnormal blood values generally develop and, as likely as not, there will be an inexorable progression of kidney destruction after that point, leading eventually to death from renal failure. It is believed that, once the kidney is significantly diseased, nephrons are lost at a constant rate due to the excessive work demands placed on those nephrons still remaining. In fact, graphic studies have shown that the course of the disease can even be roughly predicted if several creatinine measurements are taken. Creatinine is selected for this study, because it is a waste by-product of muscle breakdown and repair, and its production is nearly constant. The other two compounds most constantly monitored are urea (blood urea nitrogen) and phosphorus, but both of these are affected by diet. Essential minerals such as calcium, sodium, and potassium may also be abnormal in renal failure, but this generally occurs only after BUN (Blood Urea Nitrogen), CREAT (creatinine), and PHOS (phosphorus) are elevated several times above the normal range.

Clearly, successful management of the renal failure patient requires attention to every derangement. Nitrogenous protein wastes must be minimized, sodium must be restricted to help lower blood pressure, phosphorus must be withheld, and any anemia reversed. When dietary management fails to accomplish these objectives, specific drugs are prescribed to bind phosphorus in the intestines, minimize phosphorus and calcium release from bone, lower blood pressure, and stimulate the bone marrow to produce red blood cells. When specific drugs should be part of the management plan for any given patient is a matter of medical judgement and great debate today among veterinary clinical researchers, and much remains unanswered. Finally, it is crucial that the patient's urine is checked frequently with chemical testing and microscopy for any sign of bacteria. An animal with few nephrons cannot afford an infection, so urine testing and even bacterial culturing on a regular basis is often recommended.

This site is intended to be informative only. If your dog is suffering from a health problem,
diagnosis and treatment should be based upon consultation with your veterinarian.