28. Urinary System Disorders

CHAPTER 28. Urinary System Disorders

Dennis J. Chew




GENERAL INFORMATION






I. Upper urinary tract: Renal parenchyma, renal pelves, and ureters. Lower urinary tract: Bladder and urethra. Useful for diagnosis, prognosis, and treatment to decide how much of a urinary tract disease involves the upper urinary tract, lower urinary tract, or both


II. Upper urinary tract disorders: Chronic renal failure (CRF), acute renal failure (ARF), upper urinary tract infection (UTI), renal neoplasia, renal pelvic or ureteral obstructions, and renal bleeding


III. Lower urinary tract disorders: Bacterial UTIs, idiopathic cystitis of cats, urethral obstruction, urinary incontinence, and neoplasia of the bladder and urethra


IV. In general, animals are more likely to be sick from upper urinary tract disorders compared with those of the lower urinary tract unassociated with urinary obstruction


UPPER URINARY TRACT DISORDERS






I. Renal failure (general)




A. Excretory renal failure exists when blood urea nitrogen (BUN) and serum creatinine are above the upper normal range ( azotemia). Decide whether azotemia is prerenal, primary renal, or postrenal




1. Prerenal azotemia occurs when perfusion is reduced and nitrogenous waste accumulates in blood




a. Causes include dehydration, shock, congestive heart failure (CHF)


b. Urine should be highly concentrated. Urinary specific gravity (USG) is expected to be greater than 1.030 in dogs and 1.040 in cats


c. Urine sediment is normal; kidney size normal


2. Postrenal azotemia




a. Causes are leakage of urine into retroperitoneal or peritoneal cavities or from obstruction to outflow from both kidneys


b. USG is variable. Urinary sediment may be active with red blood cells (RBCs) or white blood cells (WBCs)


c. Imaging is necessary for diagnosis


3. Primary renal azotemia is due to renal parenchymal lesions, either acute or chronic




a. Urine cannot be highly concentrated. USG less than 1.030 in dogs and less than 1.040 in cats is expected at the same time as the azotemia


b. Urine sediment may show casts, WBCs, and proteinuria


B. Magnitude of azotemia does not distinguish prerenal, primary renal, or postrenal causes. USG is the most important factor to evaluate. Imaging is also usually necessary


II. Chronic renal failure (CRF)




A. CRF occurs with permanent loss of at least 75% of functional nephron mass as a result of chronic lesions (nephron dropout, fibrosis, tubulointerstitial nephritis [TIN]). Increased serum phosphorus is observed after 85% of nephron mass has become nonfunctional


B. Cause is usually idiopathic. Probably due to glomerular injury


C. Any age, breed, or sexual status can be affected. Risk is low for younger animals and higher for older animals. Incidence increases in those older than 10 years


D. CRF in young animals: Usually familial nephropathy or renal injury from infection or toxins. Cats rarely have familial nephropathy except for renal amyloidosis in Abyssinians and Oriental shorthairs



F. Familial renal diseases of dogs and cats




1. Amyloidosis: Abyssinian, Siamese, Oriental shorthair cat, beagle, English foxhound, shar-pei


2. Unilateral renal agenesis: Beagle


3. Glomerulopathy (basement membrane disorder): Beagle


4. Tubular dysfunction (Fanconi syndrome): Basenji


5. Tubular dysfunction (renal glucosuria): Norwegian elkhound


6. Periglomerular fibrosis: Norwegian elkhound


7. Basement membrane disorder: Bull terrier, dalmatian, Doberman pinscher, English cocker spaniel, Samoyed, Texas NAV dogs, rottweiler


8. Polycystic kidney disease: Bull terrier, Cairn terrier, West Highland white terrier, Persian cat


9. Membranoproliferative glomerulonephritis: Bernese mountain dog, soft-coated Wheaten Terrier, Brittany spaniel


10. Renal dysplasia: Soft-coated wheaten terrier, Alaskan malamute, chow chow, golden retriever, Lhasa apso, shih-tzu, miniature schnauzer, standard poodle


11. Multiple renal cystadenocarcinomas: German shepherd dog


12. Renal telangiectasia: Pembroke Welsh corgi


G. Diagnosis




1. Azotemia, submaximally concentrated urine; reduction in kidney size, irregular kidneys, nephrocalcinosis, nonregenerative anemia, chronic failure to thrive (loss of body condition, muscle mass, hair coat quality), anorexia, vomiting, depression, weight loss


2. Renal biopsy findings: Not specific


3. Renal biopsy: Not indicated in those with small kidneys


H. Progressive chronic kidney disease (CKD) eventually results in CRF




1. CKD can be discovered before CRF in those in which kidney size progressively decreases, renal mineralization progressively increases, urine concentration declines from maximal values, and proteinuria increases


2. Once a certain nephron mass has been lost from CKD, a progressive self-destructive cascade of events happens in the remaining healthier kidney that eventually results in further nephron damage (glomerulosclerosis and TIN)


3. Progressive self-propagating destruction of the chronically damaged kidney involves glomerular hypertension and glomerular hyperfiltration


4. Other mechanisms for progressive destruction: Renal mineralization and damage from uncontrolled renal secondary hyperparathyroidism


I. Treatment




1. Very little evidence exists to make decisions about treatment of CKD cases that are not yet azotemic. Nearly all of our data about treatment come from dogs and cats that are obviously azotemic


2. Dietary therapy




a. Feed a renal diet; not been determined whether this is helpful if not azotemic. May increase survival and extend the time between uremic crises


b. The two major factors of benefit: Phosphorus restriction and omega-3 supplementation


c. Protein restriction as the sole change does not protect the kidney from progression or extend the life of the dog or cat with CRF; does not reduce the workload of the kidney. Dietary protein restriction with adequate caloric intake reduces BUN, which may parallel clinical signs of uremia in some patients


d. Dietary phosphate restriction may be adequate treatment to control serum phosphorous and (PTH) concentrations in those with early CRF


3. Intestinal phosphate binders




a. Often needed to gain optimal control of serum phosphorus and serum PTH. Goal: To provide a compound that binds to intestinal phosphate, prevents its absorption, and increases its fecal excretion


b. Aluminum salts (hydroxide, carbonate): Mainstay treatment


c. Calcium salts (carbonate, acetate): Developed in human medicine to avoid toxicity from aluminum accumulation; sometimes used


d. Newer-generation medications: Sevelamer HCl and lanthanum carbonate have not yet achieved mainstream use


e. Epakatin: Veterinary product marketed for use in cats with CRF. Decreases serum phosphorus in normal cats. Reported to decrease digestibility of phosphorus in the diet


f. Phosphate binders work best when given with food or within 1 to 2 hours of food ingestions


4. Antacids




a. Gastric hyperacidity: Presumed to contribute to gastric erosions, nausea, and vomiting during CRF. Increased circulating gastrin has been documented to occur in dogs and cats with CRF as a result of decreased renal degradation of gastrin


b. Histamine (H 2) receptor blockade (e.g., famotidine, ranitidine): Usually helpful first-line treatments


c. Proton pump blockade (omeprazole) provides an option either instead of or when H 2 blockade is not effective



6. Calcitriol therapy




a. Proven benefit for survival in dogs


b. Main effect of calcitriol for patients with CRF: Decreased synthesis of PTH through genomic effects in the parathyroid gland. Excess PTH is toxic to a variety of tissues, including the kidneys


c. Calcitriol: Dosed to the effect on ionized calcium and PTH status. Doses from 2.5 to 3.5 ng/kg once daily are usually sufficient to lower PTH without increasing serum ionized calcium; can do intermittent dosing with 9 ng/kg twice weekly (every 3.5 days)


d. Serum phosphorus should be controlled to less than 6.0 mg/dL before calcitriol treatment can be safely started


7. Control of systemic hypertension




a. Important to prevent end-organ damage (eyes, brain, kidney)


b. Uncontrolled hypertension transmits excessive pressure to the glomerular capillary beds. Increased pressure contributes to glomerular hypertension and hyperfiltration, which further damages nephrons


c. ACE inhibitor: Choice for dogs, although monotherapy at the usual dose is often not effective (0.5 to 1.0 mg/kg twice daily). Increasing doses of ACE inhibitor or addition of amlodopine are provided to effect as monitored by serial measurement of blood pressure


d. Amlodopine: Drug of choice for control of systemic hypertension in cats. Most often, 0.625 mg/cat/day is safe and effective


8. Potassium salt treatment: Assess potassium status periodically (especially cats). Give potassium salts if there is persisting hypokalemia


9. Azodyl: Recently launched in the veterinary market




a. Probiotic (oral) given daily to maintain a population of colonic bacteria that metabolize nitrogenous waste


b. BUN and serum creatinine decreased in a study of a small number of cats receiving this treatment; long-term effects on progression of CRF have not been reported


10. Kremezin: Japanese product for treatment of cats with CRF. Contains granules of activated charcoal that provide nonselective adsorption of uremic toxins from the GI tract


J. Prognosis




1. Progression of CKD and CRF: Variable; slower in cats than in dogs. Many cats with CRF live for months to years. Dogs with CRF on occasion live years, but up to a year is more common with first-line treatments of diet


2. Serial analysis of serum creatinine, phosphorus, PTH, albumin, body weight, systemic blood pressure, and patient history: Necessary to determine success of treatment and disease progression


III. Acute primary (intrinsic) renal failure (AIRF)




A. AIRF: Syndrome when there has been loss of more than 75% of nephron mass, at least temporarily. Differs from CRF; possibility for healing of lesions of AIRF with recovery of renal function in some instances




1. Increased serum phosphorus often occurs early in the development of AIRF, unlike that of CRF, in which increases in PTH provide a protective lowering of serum phosphorus as nephron mass gradually proceeds


2. Progressive azotemia with or without oliguria develops as the result of some combination of vasoconstriction of the afferent arteriole, increased tubular pressure from intratubular obtruction or extraluminal compression, tubular backleak, or failure to filter due to changes in the character of the glomerular filter


B. Renal lesions of AIRF




1. Classically acute tubular necrosis (ATN); spectrum of necrosis to subtle degeneration. ATN is secondary to either ischemic or nephrotoxic causes


2. Acute interstitial nephritis also can create AIRF secondary to infectious causes (allergic reaction rarely). Acute interstitial nephritis in dogs is classically associated with leptospirosis


C. Ischemic causes of ATN and AIRF




1. Systemic hypotension is not necessary for the development of tubular lesions. Renal blood supply determines if lesions develop


2. Causes include dehydration, trauma, anesthesia, sepsis, heat stroke, pigment nephropathy (hemolysis from immune-mediated hemolytic anemia, coral snake envenomation, bee sting, myoglobinuria), ACE inhibitors, shock, hemorrhage, surgery, burns, hypothermia, nonsterodal antiinflammatory drugs (NSAIDs), acute papillary necrosis (medullary renal amyloidosis, Fanconi syndrome)



E. AIRF: Three classic phases—latent or incipient phase, maintenance, and recovery




1. Latent phase: Time from initial exposure to the nephrotoxin or ischemic event until there is evidence for renal injury (cylindruria, renal epithelial cyturia, renal tubular enzymuria, submaximal urine concentration, decreased glomerular filtration rate [GFR] before azotemia)




a. Animals in this phase are usually asymptomatic and will be discovered only if there is suspicion for the development of AIRF while in the hospital and being treated with drugs with known nephrotoxic potential


b. Removal of the inciting cause stops further renal injury


2. Maintenance phase: Develops after a critical mass of lethal renal cell injury has occurred




a. Azotemia has developed by this time and does not immediately respond to correction of dehydration or volume expansion


b. Removal of the inciting phase does not result in correction of azotemia


c. This is a fixed phase of excretory renal failure that can last 1 to 3 weeks, or it may last forever (when no healing occurs)


d. Some will be oliguric or anuric (e.g., EG intoxication); others may have polyuria (e.g., aminoglycoside intoxication)


3. End of maintenance phase: When the patient dies or is euthanized, returns to normal renal function based on BUN and creatinine, or heals as a renal cripple with CRF of varying magnitude




a. Some patients return to a normal BUN and creatinine. GFR may still be lower than normal if measured


b. Maximal ability to concentrate urine may or may not be restored


F. Treatment




1. Most important aspect of treatment: Optimal IV fluid therapy. With inadequate fluid therapy, the kidneys do not receive enough perfusion, allowing the development of further lesions of ATN from ischemia. Excess fluid therapy results in development of overhydration, CHF, pulmonary edema, and death




a. Measurement of urine output is imperative during the first 24 to 48 hours


b. Normal urine output is 0.5 to 1.0 mL/kg/h; if on IV fluids, 2.0 to 5.0 mL/kg/h is expected. Less than 2 mL/kg/h defines oliguria in patients on IV fluids


2. If oliguria or anuria persists after correction of dehydration, increase urine flow using some combination of mannitol, furosemide, or dopamine


3. If urine flow is not increased after diuretic treatments, stop diuretics and decrease IV fluids to avoid the development of overhydration and allow time for natural healing and resolution of AIRF if possible


4. Dialysis improves prognosis for survival and renal recovery; early rather than late dialysis treatments are more effective in providing a beneficial outcome. Hemodialysis is available at a few regional centers in the United States; peritoneal dialysis is more widely available and less expensive


G. Prognosis varies with the specific cause of the AIRF. In general, the higher the level of the azotemia during the maintenance phase, the poorer the prognosis. Overall, leptospirosis has the best prognosis for survival and recovery of normal renal function; EG cases with azotemia and oligo-anuria have the worst prognosis.


H. EG intoxication




1. Occurs following ingestion of 4 to 13 mL/kg in dogs and 1.5 mL/kg in cats; can be lethal. EG is transformed to cytotoxic metabolites in the liver by alcohol dehydrogenase. The half-life of EG is less than 12 hours in dogs and considerably shorter in cats


2. Diagnosis is based on observation of ingestion, finding a source for possible ingestion, and acute onset of alcohol-like inebriation. Painful kidneys and muscles may be detected on physical examination. Finding some combination of metabolic acidosis that may be severe, hyperphosphatemia out of proportion to the azotemia observed, high anion gap, and very high osmole gap are highly supportive for the early diagnosis of EG toxicity. A positive colorimetric reaction on the EG test kit (in-house method) provides convincing evidence for this diagnosis. Chromatographic techniques are available for definitive diagnosis using blood and urine samples, but it usually takes days to get results


3. Polyuria and polydipsia can be intense shortly after ingestion of EG and are often followed by development of oliguria and then anuria that persists despite all treatments



5. Treatment




a. In dogs, 4-methylpyrazole (4-MP) is the definitive antidote for treatment before EG has been completely metabolized. 4-MP antagonizes the activity of alcohol dehydrogenase, which lessens biotransformation of EG to toxic metabolites. Effective after ingestion of a lethal dose up to at least 5 hours in most dogs and up to 8 hours in many. After 8 hours following ingestion, most EG has been transformed to its toxic compounds


b. Cats require much higher doses of 4-MP than dogs; sedation is a side effect at these high doses


c. Ethyl alcohol: Antidote of choice before 4-MP was developed in both dogs and cats; competes with EG for metabolism by alcohol dehydrogenase. Severe depression from ethyl alcohol is a major side effect; it also adds to dehydration. Respiratory depression can cause death


d. Hemodialysis of dogs for 6 to 9 months has been effective for recovery of renal function in some dogs that were anuric. Prognosis for survival in anuric patients without access to dialysis is near zero


I. Leptospirosis




1. Leptospirosis is a systemic disease of dogs that can cause AIRF from acute to subacute interstitial nephritis. Infection usually follows mucosal penetration of organisms from drinking water that has been contaminated with urine from infected carriers


2. Vaccination against serovars canicola and icterohemorrhagiae has greatly lessened clinical disease with these serovars. Clinical syndromes are usually due to “atypical” serovars, in which vaccines have not been administered to most dogs (pomona, grippotyphosa, Bratislava in the United States)


3. Encroachment of wildlife into suburban living spaces accounts for infections with atypical serovars; exposure to farm animals also accounts for infection with some serovars


4. Infections with serovars canicola and icterohemorrhagiae classically have changes in liver enzymes at the same time renal failure is discovered. Atypical serovars do not typically increase liver enzymes; if elevated, liver enzymes may not be increased at the same time as increased BUN or creatinine


5. Oliguria initially is prerenal as a result of systemic effects of the infection; as renal lesions accrue, oliguria from primary renal mechanisms predominate. Urinary concentration is initially high and becomes progressively less concentrated. USG is often in the isosthenuric range when AIRF is diagnosed


6. Treatment




a. Penicillin: Drug of choice to eliminate leptospiral organisms from most of the body; doxycycline is the treatment of choice to rid dogs of the renal carrier state.


b. Supportive treatment with IV fluids for 1 to 2 weeks in addition to penicillins. Short-term dialysis may be needed in those with oligoanuria and high-level azotemia


7. Prognosis is generally good for AIRF secondary to leptospiral infection when penicillins are started early enough


J. Parenteral antibiotics




1. Occasionally cause AIRF from ATN. All IV antibiotics can at times cause AIRF, especially when given rapidly at high doses. Aminoglycoside toxicity is most common; most reports are from gentamicin in dogs or cats, but all aminoglycosides are nephrotoxic and capable of inducing AIRF


2. Aminoglycoside nephrotoxicity has become less common because of the development of the fluoroquinolones for treatment of serious bacterial infections


3. Aminoglycosides are prescribed in complicated medical conditions, often those that are life-threatening


4. Giving the total daily dose of aminoglycoside once daily rather than in divided doses reduces renal exposure to this nephrotoxin. This method of dosing may contribute to the decreased incidence of aminoglycoside nephrotoxicity


5. A “cast watch” can be useful to detect renal damage before BUN and creatinine increase; reduction in USG and increases in excretion of urinary enzymes also precede increases in BUN and serum creatinine


K. Lily intoxication




1. Creates a specific syndrome of AIRF in cats, but not in dogs. Indoor cats are particularly attracted to this plant


2. All parts of the lily are toxic, and only a small part need be eaten for the nephrotoxic effects to be seen. Detection of plant pieces in vomitus or feces should increase the suspicion for lily toxicity


3. Severe azotemia and oligoanuria can be seen in this form of AIRF. Despite massive azotemia, some cats have recovered with medical treatment for several weeks


4. There is no antidote; the specific toxin has yet to be isolated


L. Raisin or grape ingestion




1. Cause AIRF in dogs with or without hypercalcemia; toxicity not reported in cats


2. Gastric decontamination is recommended, even for small amounts if there are GI signs


3. Dehydration from GI signs is common: IV fluid support may be needed for up to 1 week, longer if already in renal failure. Prognosis is fair to good when supportive treatment instituted early


4. No antidote available; the toxic principle is not known


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Apr 6, 2017 | Posted by in GENERAL | Comments Off on 28. Urinary System Disorders

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