Haemodynamic Changes

Pro-BNP

Utilising pro-BNP it was shown that dogs with babesiosis have reduced cardiac function and that the dysfunction becomes more severe as the disease severity increases. This myocardial dysfunction occurs either earlier and/or is independent of myocardial damage, which can be subtler.

Troponin

In canine babesiosis it has been shown that troponin I is a sensitive marker of myocardial injury with the magnitude of elevation of troponin I appearing to be directly proportional to the severity of the disease. Dogs dying of canine babesiosis with histological evidence of myocardial lesions had higher concentrations of troponin I than did dogs that survived.

Blood Pressure

Dogs with severe and complicated babesiosis are frequently presented in a state of collapse and clinical shock, with the shock resembling the hyperdynamic phase of septic shock. It has been shown that hypotension occurs frequently in babesiosis and that the presence and severity of hypotension increases with increased disease severity. It is likely that hypotension in babesiosis is a combination of vasodilation, reduced vascular volume due to increased vascular permeability and/or dehydration, and myocardial depression. Myocardial infarction can result in vascular pooling and myocardial depression. The hypotension can also play a role in the pathophysiology of the disease as it has been hypothesized to facilitate parasite sequestration within the capillary beds.

ECG

Dogs with babesiosis can show a variety of arrhythmias and ECG abnormalities. Arrhythmias include SA block, sinus arrest, first- and second-degree AV block, ventricular tachycardia, and VPCs. ECG changes include low R-amplitude, prolonged QRS, ST deviation, large T waves, and notching of the R wave. These ECG changes have been described in dogs with myocardial infarction, ischaemia and in Chagas disease. Although bradycardia and irregular rhythm in dogs may be poor prognostic indicators, in general the ECG changes do not appear to be related to disease severity or to pathological changes and thus the clinical value of ECG monitoring in canine babesiosis is limited. The only exception to this is the presence of VPCs, as they appear to be associated with an elevated troponin I concentration.

Cardiac Pathology

Macroscopic cardiac lesions that have been described in dogs with babesiosis include pericardial effusion and pericardial, epicardial and endocardial haemorrhage, involving one or more of the chambers. Documented cardiac histopathology changes are haemorrhage, necrosis, inflammation and fibrin microthrombi in the myocardium.

Renal Function

Acute renal failure (ARF) is an uncommon complication of babesiosis and typically presents as anuria or oliguria despite adequate hydration. Renal failure is diagnosed on the basis of ongoing evaluation of urine volume, urine analysis and degree of azotaemia. The reported incidence of ARF in canine babesiosis is 2.2%.

Urine Analysis

Urine analysis typically shows hypersthenuria, bilirubinuria, haemoglobinuria, proteinuria, granular casts, and renal tubular epithelial cells (RTE). This evidence of renal damage is common in both complicated and uncomplicated cases, but does not necessarily reflect or predict renal failure.

Proteinuria

Proteinuria appears to be common in canine babesiosis and occurs within 24 hours of the first appearance of parasites in the blood. In later stages of the infection, there is evidence of tubular damage in the form of granular and hyaline casts. Although mice with babesiosis develop immune-complex-induced mesangiopathic glomerulonephropathy, canine babesiosis has not been associated with glomerulonephropathy, and the degree of proteinuria is more consistent with tubulointerstitial disease.

Urine Sediment

The presence of RTE cells in the urine sediment can indicate renal damage due to hypoxia, hypoperfusion, or toxic damage. Renal hypoxia results in rounding and retraction of RTE cells with a disruption of actin microfilaments, as a result of which a large number of viable RTE cells are sloughed into the urine. Acute renal hypoxia has also been shown to induce apoptotic changes. This may explain the lack of correlation between urine enzyme activity and the presence of RTE cells.

Urinary Markers

It has been shown that dogs with babesiosis have significantly higher concentrations of urinary immunoglobulin G and urinary C-reactive protein and would appear to be superior to specific gravity, and serum urea and creatinine concentrations for the early detection of renal dysfunction in dogs with babesiosis.

Although urine enzyme (GGT and ALP) activity is both an early and persistent indicator of renal tubular damage, in canine babesiosis changes in urine enzyme activity appear to be variable and minimal, thus making them not a useful diagnostic test.

Fractional Clearance of Sodium

The majority of sodium is actively reabsorbed from the proximal convoluted tubule, resulting in passive water reabsorption with further reabsorption occurring in the distal convoluted tubule and collecting duct. In canine babesiosis, low fractional clearance of sodium is a common finding, which can be interpreted as either renal retention of sodium secondary to aldosterone secretion or inhibition of prostaglandins, or as a result of activation of the renin-angiotensin-aldosterone system, in response to renal arterial hypotension. The well-concentrated urine in all dogs with babesiosis can also be attributed to sodium and water retention.

Serum Urea and Creatinine

In babesiosis, an elevated serum urea alone is an unreliable indicator of renal insufficiency, as a disproportionate rise in urea, compared with creatinine, occurs. The phenomenon has been attributed to catabolism of lysed erythrocytes, resulting in an increased ammonia load on the liver and consequent increased urea production, but could also be associated with gastrointestinal haemorrhage, ingestion of a high protein meal, more generalized protein catabolism resulting from a febrile, inflammatory illness. In complicated babesiosis, there is often an elevated serum urea associated with a concomitant increase in the serum creatinine, which could reflect decreased renal blood flow, possibly as a result of decreased blood pressure, decreased myocardial function, and/or hypovolaemia.

Serum Electrolytes

Hyponatraemia occurs in approximately 17% of dogs with babesiosis, which may be caused by a decreased response to water load, attributed to peripheral vasodilatation which results in a decreased effective blood volume leading to the release of vasopressin and noradrenalin, increased renin activity and decreased renal perfusion.

Dogs with babesiosis-induced hypokalaemia have a normal to increased fractional clearance of potassium, which is an abnormal response and could be indicative of early renal tubular dysfunction or as a response to alkalosis. Hyperkalaemia in babesiosis is often associated with ARF. As canine red blood cells are much lower in potassium than human red blood cells, hyperkalaemia is unlikely to occur as a result of haemolysis in the dog.

Cystatin-C

Cystatin-C has been proposed as a more sensitive marker for reduced glomerular filtration rate than creatinine. In a study in falciparum malaria, cystatin-C was compared with creatinine and it was concluded that renal disease appears to have been underestimated using creatinine as a common screening test. In one study in canine babesiosis both the mean and median serum cystatin-C concentrations were within reference range.

Renal pathology

Babesiosis can result in a kidney that is swollen and dark in colour, with red-brown urine in the bladder. Microscopically the RTE cells are swollen with haemoglobin droplets and small vacuoles with necrosis evident in severe cases. Multiple haemoglobin casts are also present in the nephron lumen. These morphologic lesions have been attributed to anaemic hypoxia resulting from erythrocyte destruction. However, in cases of complicated babesiosis with elevated creatinine, the mean haematocrit is significantly higher, making hypovolaemia a more likely cause than anaemia for the renal failure described in this disease.

Role of Haemoglobin and Methaemoglobin

Renal changes in babesiosis were referred to as haemoglobinuric nephropathy; however, one study showed that haemoglobinuria, of the magnitude seen in canine babesiosis, did not induce a significant nephropathy, regardless of whether or not concomitant anaemia was present. That study also showed that the GFR was reduced in the groups of dogs that were rendered anaemic to the same degree that would occur in severe cases of babesiosis.

In one study, dogs with naturally occurring babesiosis had significant urine methaemoglobin with no evidence of blood methaemoglobin, implying that the urinary methaemoglobin was either produced in the kidney or possibly by oxidation of haemoglobin to methaemoglobin in the bladder. Methaemoglobin has been shown experimentally to be toxic.

Conclusion

The renal changes evident in canine babesiosis are minimal and could be consistent with hypoxia, reduced GFR, or reduced cardiac output. The combination of reduced GFR, anaemic hypoxia, and methaemoglobin can all act synergistically to cause renal damage.

Renal haemodynamics are also much more likely to be abnormal when cardiac dysfunction is present. Reduced renal blood flow and glomerular filtration rate are evidence of redistribution of blood flow that commonly occurs in early heart failure. Thus the renal changes in canine babesiosis are most likely secondary to cardiac dysfunction and the cardiac complications are thus more important.