Introduction

Renal transplantation is currently an accepted treatment option for cats diagnosed with end-stage renal disease, and if successful, the technique appears to improve the quality of life and prolong survival times compared to the medical management of the disease.¹ In an attempt to decrease morbidity and mortality rates during the perioperative and postoperative periods, a thorough evaluation of both physical and biochemical parameters including evaluation for cardiovascular disease is critical in determining a patient’s candidacy for the procedure.

In humans, cardiovascular disease is the leading cause of death for patients with end-stage renal disease on waiting lists for transplantation^2–5 and for those who have already undergone the procedure.^6–8 Cardiac involvement starts early in this patient population, with alterations in both systolic and diastolic myocardial function identified in even mild to moderate cases of chronic kidney disease.⁹ Coronary artery disease (CAD) can rapidly develop and progress with significant vascular calcification, atherosclerosis, and reduced vascular compliance. The increase in vascular stiffness associated with both coronary and systemic arteries contributes to systemic hypertension and left ventricular hypertrophy often identified in this patient population.^10–12 Progression of myocardial hypertrophy and fibrosis can alter left ventricular relaxation and compliance, ultimately resulting in diastolic dysfunction.¹³ Cardiomyopathy (CM) and ischemic heart disease are the most frequent causes of death identified.^14–16 For this reason, a thorough pretransplant evaluation for significant cardiovascular disease is commonly performed in humans on the transplant waiting list to help identify patients with unstable cardiac conditions as well as implement therapies to reduce the incidence of major adverse cardiovascular events in the perioperative and postoperative periods.

Although a wealth of information exists in the human medical literature regarding cardiac screening, risk assessment, and the predictive value of various echocardiographic findings on perioperative complications and survival, limited information currently exists in the veterinary literature. In 1 feline study,¹ left ventricular wall thickness was identified as being significantly associated with perioperative mortality and preoperative hypertension negatively influenced overall survival. The authors of this study did comment that their results may have been skewed since cats determined to have significant heart disease were excluded as transplant recipients. In a second study¹⁷ of 84 potential transplant recipients, 78% of cats were found to have abnormalities on echocardiographic examination, with the most common changes being septal and papillary muscle hypertrophy. The authors of this study suggested that these changes might be related to chronic uremia, hypertension, age, or early changes of hypertrophic CM. In that study,¹⁷ an analysis of preoperative echocardiographic changes found no significant predictors of 1-month survival in transplant recipients.

Prior to 1998 at the authors’ facility, the presence of structural heart disease in cats with end-stage renal disease was considered evidence of primary CM and an absolute contraindication for transplantation. Since that time, because of the number of cases presenting with echocardiographic changes and the greater understanding of the effects of uremia on the myocardium and cardiac function, our program has “pushed the envelope” on performing transplants on cats that would have otherwise been disqualified as candidates with consistently positive results. Based on our clinical experience, it is unclear above what threshold of cardiac disease it becomes a contraindication to accept a candidate for the procedure.

For this reason, the goal of the study reported here was to retrospectively evaluate preoperative historical data and cardiovascular-related screening data for predictors of survival to discharge and long-term survival in feline renal allograft recipients from 1 institution. As uremia may contribute to the development of cardiovascular disease, biochemical data were also evaluated. We hypothesized that biochemical parameters indicative of severe uremia would be associated with the presence of cardiac remodeling. We further hypothesized that the presence of echocardiographic changes would not be associated with decreased survival following renal transplantation.

Materials and Methods

The records from 166 cats that underwent renal allograft transplantation at the University of Pennsylvania between 1998 and 2018 were reviewed. Screening prior to transplantation typically included laboratory tests (CBC, serum biochemistry panel, blood typing, and thyroid function testing), evaluation of the urinary tract (urinalysis, urine culture, urine protein-to-creatinine ratio, abdominal radiography, abdominal ultrasonography, and renal biopsy diagnosis), evaluation for cardiovascular disease (thoracic radiography, electrocardiography, echocardiography, and blood pressure evaluation), and screening for infectious diseases (antibody or antigen testing for FeLV and FIV respectively, and serologic testing [IgG and IgM] for Toxoplasma gondii). For each cat, information on signalment, weight and body condition score at time of transplantation, erythropoietin analog and transfusion administration, need for hemodialysis, number of surgical procedures, biopsy diagnosis, and survival time were recorded. Complete blood count and serum biochemistry values including PCV, total WBC, platelet counts, BUN, creatinine, phosphorus, calcium, potassium, and albumin values obtained in the 7 days prior to transplantation were recorded. If multiple samples were collected during this time, the results of preoperative laboratory testing obtained in closest proximity to the transplant date were used. For biopsy samples of the native kidneys performed prior to transplantation by the referring veterinarian or at the time of the surgical procedure, routine histologic examination was performed. Samples were fixed in neutral-buffered 10% formalin and embedded in paraplast. Sections of kidneys (5 mm) were stained with H&E for evaluation.

Cardiac assessment included auscultation to detect a heart murmur or arrhythmia and pre- and postoperative systolic blood pressure measurements. Hypertension was defined as a systolic blood pressure > 170 mm Hg. For cats with preoperative thoracic radiographs, a single cardiologist measured a vertebral heart size and evaluated images for pulmonary vessel enlargement and signs of congestive heart failure including pleural effusion or pulmonary edema. Evidence of soft tissue mineralization involving cardiac and aortic structures was also documented. Preoperative echocardiographic measurements using either M-mode or 2-D images from the right parasternal short axis view including diastolic interventricular septal wall thickness (IVSd), diastolic left ventricular posterior wall thickness (LVPWd), left ventricular internal diameter in systole (LVIDs), left ventricular internal diameter in diastole (LVIDd), fractional shortening (FS), aorta diameter (AoD), left atrial diameter (LAD) short-axis size, and LAD:AoD ratio were recorded.

Results

The demographics and clinicopathologic data of the patient population (Table 1) and cardiac data (Table 2) are shown. The population primarily consisted of adult male DSH cats, with 66.3% (110/166) diagnosed with IRIS stage 4, 30.1% (50/166) diagnosed with IRIS stage 3, 2.4% (4/166) diagnosed with IRIS stage 2, and 1.2% (2/166) diagnosed with IRIS stage 1 based on the IRIS chronic kidney disease staging guidelines. Eighty-nine percent of cats (148/166) were anemic. Eighty-one percent (132/163) of cats received 1 or more transfusions preoperatively to treat their anemia (1 transfusion [53], 2 transfusions [60], 3 transfusions [13], 4 transfusions [5], and 6 transfusions [1]). Purebred cats included 12 Siamese, 5 Persian, 4 Abyssinian, 3 Maine Coon, 3 Himalayan, 2 Tonkinese, and 1 of each of the following breeds: Bombay, Balinese, Cornish Rex, Oriental shorthair, Ragdoll, and Russian blue. The most common indication for transplantation was chronic interstitial nephritis.

Twenty percent (32/158) of cats were diagnosed with hypertension during the preoperative hospitalization period, and 45.6% (62/133) were diagnosed with hypertension at the time of discharge. Nine percent (14/158) of cats diagnosed with preoperative hypertension were treated with antihypertensive medication including amlodipine (12 cats; 1.25 mg, q 12 h), propranolol (1 cat; 2.5 mg, q 12 h), and benazepril (1 cat; 2.5 mg, q 24 h). One hundred forty-eight cats had preoperative auscultation findings recorded. Systolic murmurs were reported in 67% (99/148) of cats; 33% (49/148) of cats had no murmurs auscultated. In cats with heart murmurs auscultated, the proportion for each grade was grade I (n = 19; 19.2%), grade II (41; 42.4%), grade III (31; 18.2%), and grade IV (4; 4%); 4 murmurs were not graded (4%). Twenty five of 148 (16.9%) cats had a gallop rhythm, and 8 of 163 (4.9%) cats had ventricular premature complexes identified.

Thoracic radiographs were available for 110 cats. Abnormal findings were identified in 64 of 110 (58%) cats and included cardiomegaly (41/110 [37.2%]), aortic mineralization (18/110 [16.4%]), pleural effusion (11/110 [10%]), alveolar infiltrate (9/110 [8.1%]), and hyperinflated lungs (4/110 [3.6%]). Prior to transplantation, 15 of 110 (13.6%) cats were diagnosed with congestive heart failure. Four of 15 (27%) cats diagnosed with congestive heart failure died prior to discharge compared to 5 of 95 (5%) without congestive heart failure. There were no significant effects of abnormal findings identified on thoracic radiographs, including radiographic signs of heart failure (P = 0.65; OR, 1.51, 95% CI, 0.62 to 2.13) on survival following discharge (Figure 1).

View Full Size

Kaplan-Meier curves of 110 cats undergoing renal transplantation, including 95 cats without congestive heart failure at time of presentation (solid blue line) and 15 cats with congestive heart failure (dashed red line; P = 0.65).

Citation: Journal of the American Veterinary Medical Association 260, 12; 10.2460/javma.22.03.0120

• Download Figure
• Download figure as PowerPoint slide

Echocardiographic data were available for 137 of 166 (82.5%) cats; not all cats had all parameters recorded. Mitral regurgitation was present in 32 of 135 (23.7%) cats, and tricuspid regurgitation was present in 30 of 135 (22.2%) cats. Echocardiographic parameters, including IVSd, LVPWd, LVIDd, LVISs, FS, AoD, LAD short axis, and LAD:AoD ratio, were evaluated. Of cats with available data, 45 of 137 (32.8%) cats had hypertrophy of the IVSd (median, 4.8 mm; IQR, 4.3 to 5.5 mm; range, 3.0 to 6.9 mm; normal, 3.7 to 5.3 mm), while 11 of 137 (8%) of cats had reduced IVSd measurements. A total of 72 of 137 (52.6%) cats had hypertrophy of the LVPWd (median, 4.8 mm; IQR, 4.3 to 5.4 mm; range, 2.8 to 9.0 mm; normal, 3.4 to 4.8 mm); 2 of 137 (1.5%) cats had decreased LVPWd measurements. Thirty of 133 (22.6%) cats had a decrease in LVIDd, while 31 of 133 (23.3%) cats had an increase in LVIDd (median, 15.2 mm; IQR,14 to 17 mm; range, 10 to 28; normal, 13.8 to 17 mm). Twenty six of 135 (19.3%) cats had a decrease in LVIDs, while 17 of 135 (12.6%) cats had an increase in LVIDs (mean, 7.1 mm, SD 1.9 mm; range, 2.7 to 12 mm; normal 5.6 to 9.4 cm). Fractional shortening was decreased in 14 of 134 (10.4%) and increased in 24 of 134 (17.9%) of cats (median, 54.0%; IQR, 47% to 60%; range, 32% to 80%; normal, 42% to 64%). Aortic diameter was considered decreased in size in 16 of 132 (12%) cats and increased in size in 21 of 132 (15.9%) cats (mean, 9.5 mm; SD 1.3 mm; range, 4.8 to 1.31 mm; normal, 8.1 to 10.9 mm). The LAD in short-axis view was decreased and increased in 8 of 31 (6.1%) and 51 of 131 (38.9%) cats (median, 13.3 mm, IQR 12 to 15.1mm, range, 7.1 to 22 mm; normal, 9.6 to 13 mm), respectively. The LAD:AoD ratio was increased in 64 of 131 (48.9%) cats (median, 13.3 mm; IQR, 12 to 15.1 mm; range, 6 to 26 mm; normal, 10.1 to 13.9 mm) and decreased in 8 of 131 (6.1%) cats.

Results of univariable Cox regression are shown (Table 3). Variables subsequently selected for multivariable analysis included age, potassium, PCV, LVPWd, and hypertension at discharge. No combination of variables resulted in a regression other than age as the single significant variable. For every 1 year of age, the risk of death increased by 11% (95% CI, 6% to 17%). When considering 2 groups of cats, cats > 8 years of age at time of transplantation were 79% (95% CI, 27% to 153%) more likely to die at any time after transplantation than cats who were < 8 years of age. Median survival for cats > 8 years was 520 days (IQR, 383 to 832 days, range, 2 to 3,560 days) and 982 days (IQR, 579 to 1579 days; range, 2 to 4,964 days) in cats < 8 years (P = 0.0007).

For all cats, there were no significant correlations among biochemical variables, PCV, and echocardiographic parameters except a very weak positive correlation between creatinine and IVSd (r = 0.182; P = 0.03). A weak correlation was also identified between PCV and LVID (r = 0.177; P = 0.046). Cats diagnosed with preoperative hypertension had a significantly greater IVSd (P = 0.0005; median. 5.4 mm; IQR. 4.8 to 6.3) and left ventricular wall thickness (LVPWd: P = 0.0005, median, 5.4 mm; IQR, 4.9 to 6.8) compared to normotensive cats (IVSd [median, 4.8 mm; IQR, 4.1 to 5.3] and LVPWd [median, 4.8 mm; IQR, 4.2 to 5.3 mm]), but similar LAD:AoD ratio values. There was no association between preoperative hypertension (P = 0.75) and the presence (n = 15) or absence (95) of congestive heart failure. The LAD:AoD ratio was not significantly larger in cats diagnosed with congestive heart failure (P = 0.16; median, 15.5, mm; IQR, 13 to 16 mm) compared to those without congestive heart failure (median, 13.4 mm; IQR, 12 to 15 mm). Fifty-two percent (71/137) of cats were noted to have cardiac remodeling in the echocardiographic report. Cats with remodeling (9.3 years) were significantly older than those without (6.8 years).

Thirteen of 166 (7.8%) of cats required a second transplant prior to discharge from the hospital. Reasons for retransplantation included infarction (n = 4), technical complications (2), venous thrombosis (2), rejection (1), neoplasia of allograft (1), cyclosporine nephrotoxicity (1), urine leakage from allograft (1), and retroperitoneal fibrosis (1). The need for a second transplant was not associated with survival to discharge or long-term survival (P = 0.51; OR, 1.22; 95% CI, 0.67 to 2.21). One hundred fifty-two (91.6%) cats survived to hospital discharge, and 14 (8.4%) cats died prior to discharge from the hospital. Twenty (12.1%) transplant recipients were censored (still alive or known to be alive at the time of their last follow-up examination). The median survival time posttransplantation for all cats was 697 days (95% CI, 520 to 982).

Discussion

For humans diagnosed with end-stage renal disease, cardiovascular disease, including CAD and CM, is the leading cause of morbidity and mortality in patients undergoing hemodialysis prior to transplantation and those that have already undergone the procedure. In fact, for patients being treated with hemodialysis, cardiovascular disease accounts for 40% to 50% of all deaths^15,16,18,19 in this patient population, and following transplantation, cardiovascular complications are the leading cause of mortality and account for almost half of all deaths in patients with a functioning graft.^3,20

Both hemodynamic and nonhemodynamic abnormalities that occur in patients with end-stage renal disease are thought to play a role in cardiac structural and functional changes resulting in dysfunction. Hemodynamic abnormalities include increased afterload, decreased vessel compliance, and hypertension. Nonhemodynamic derangements include uremia, anemia, secondary hyperparathyroidism, and overactivity of the renin-angiotensin system.²¹ Additionally, dialysis-related factors including catheter access related infections, the presence of endotoxin in the dialysate, and incompatibility between the patient’s blood and dialyzer can result in chronic inflammation in patients with end-stage renal disease, further contributing to CAD.²²

Although a wealth of knowledge exists regarding the pathophysiological relationship between the kidney and heart (cardiorenal syndrome) and how acute or chronic dysfunction of 1 organ can induce dysfunction of the other is well described in humans, limited information exists in the veterinary literature characterizing this relationship. Recently, a consensus group has defined cardiorenal syndrome in veterinary patients as cardiovascular renal disorders and suggests the understanding of this relationship is still in its infancy,²³ but there is little direct evidence in cats that primary kidney disease results in cardiovascular dysfunction.^24,25

Renal transplantation is currently an accepted treatment option for cats with end-stage renal disease, and successful transplantation can result in resolution of clinical signs, improvement in quality of life, and prolonged survival times compared to the medical management of the disease.¹ At presentation for transplantation at the author’s facility, approximately two-thirds of patients present in IRIS stage 4 and abnormalities on echocardiographic examination are commonly identified during the screening process. Despite these findings, in the author’s experience, cardiovascular complications during the perioperative and the postoperative period are rarely identified. The discrepancy between humans and cats may be related to common risk factors in human patients not identified in cats presenting for transplantation, including hemodialysis treatment for > 1 year, diabetes mellitus, smoking, and hyperlipidemia.^26,27 Additionally, CAD, which is the most frequent form of cardiovascular disease identified in human chronic renal failure patients and the leading cause of morbidity and mortality, is rarely identified in cats. For this reason, determining the predictive value of cardiovascular-related screening on perioperative complications and survival following renal transplantation was the primary goal of the present study. Additionally, preoperative historical and biochemical data as well as its relationship to echocardiographic changes were also evaluated.

In the current study, only 9 cats required hemodialysis for stabilization prior to transplantation, and hemodialysis treatment was not significantly associated with survival to discharge or long-term survival. This finding is in stark contrast to results in human medicine, which report prospective patients on hemodialysis to have a 35 times higher mortality from cardiovascular complications compared to the general population²⁸ and cardiovascular disease accounts for approximately 40% to 50% of deaths in patients undergoing hemodialysis treatment prior to transplantation.²⁹ The reason for this difference may be related to a significant difference in the duration of dialysis treatment between humans and cats, with the majority of human patients receiving hemodialysis for months to years while waiting for a donor kidney to become available, resulting in hemodialysis risk factors contributing to the progression of CAD. Since donor availability is rarely a limiting factor in feline renal transplantation, dialysis treatment is performed in cats to stabilize them for anesthesia and surgery by correcting life-threatening electrolyte abnormalities and improving their uremia, but cats rarely require hemodialysis treatment for longer than a few weeks prior to transplantation.

Preoperatively, 89% of cats were anemic and 28% of cats in this study received an erythropoietin analog as part of their medical management prior to surgery. Eighty-one percent of cats (132/163) received 1 or more transfusions preoperatively. In human transplant recipients, anemia induces left ventricular dilation and compensatory left ventricular hypertrophy and an association of anemia with CAD, myocardial infarction, CHF, and mortality has been identified.^30,31 Partial correction of anemia secondary to erythropoietin treatment has resulted in improvement, but not normalization of left ventricular mass in human patients.³² Because echocardiography was not performed prior to and following initiation of erythropoietin analog treatment or transfusion administration, it is unclear whether similar improvements would occur in feline patients. Regardless, neither the presence of anemia prior to transplantation nor the use of an erythropoietin analog or transfusion administration was associated with survival to discharge or long-term survival.

At the time of presentation, 15 cats in the current study were diagnosed with congestive heart failure. Abnormalities on thoracic radiographs were identified in 58% of cats, with the most common finding being cardiomegaly. Other findings included pleural effusion, the presence of alveolar infiltrate, hyperinflated lungs, and aortic mineralization. Although the LAD and LAD:AoD ratio was increased in approximately 40% and 50% of cats respectively, the LAD:AoD ratio size was not significantly larger in cats diagnosed with congestive heart failure compared to those without congestive heart failure. Careful management of fluid therapy can be challenging in hospitalized feline patients with end-stage renal disease, as these patients have difficulty regulating fluid volume which can result in volume overload particularly in patients with underlying heart disease or severe anemia.^25,33 Frequent reassessment and adjustment of fluid and electrolyte balance is critical as the clinical picture of the patient changes. In 1 report³⁴ of human diabetic patients undergoing renal transplantation, evidence of cardiomegaly or congestive heart failure on preoperative imaging did not impact survival following surgery. In our study, there were no significant effects of abnormal findings identified on thoracic radiographs, including evidence of heart failure on survival following discharge. Further investigation is necessary since the number of patients in the current study that presented with congestive heart failure was small.

In the present study, 20% of cats were hypertensive in the preoperative period and 46.6% of cats were hypertensive at discharge. This compares to a previous study that reported hypertension in 18% of cats prior to surgery and in 62% of cats in the postoperative period.³⁵ The increased incidence of hypertension following renal transplantation is likely multifactorial. Immmunotherapy currently used in the feline renal transplant recipient consists of a combination of the calcineurin inhibitor cyclosporine and the glucocorticoid, prednisolone. Cyclosporine can cause arteriolar vasoconstriction, resulting in an increase in peripheral vascular resistance. Additionally, cyclosporine can cause extracellular fluid expansion by activating the renin angiotensin system, reducing glomerular filtration rate, and inactivating atrial natriuretic peptide. Steroid use can impair urinary salt and water excretion, further contributing to the hypertension.³⁶

In cats, systemic hypertension associated with end-stage renal disease can result in myocardial hypertrophy and progressive cardiovascular dysfunction.^24,37,38 In the current study, hypertrophy of the IVSd and LVPWd was present in approximately 33% and 53% of cats, respectively, and cats diagnosed with preoperative hypertension had significantly greater IVSd and left ventricular wall thickness in diastole (LVPWd) compared to normotensive cats. Despite these changes identified on echocardiographic examination, neither preoperative hypertension nor hypertension at discharge was associated with survival following discharge. This finding is in contrast to 1 previous feline study¹ that indicated preoperative hypertension negatively influences overall survival in the feline renal transplant recipient. Additionally in the present study, there was no association between preoperative hypertension and the presence of congestive heart failure. In human patients with end-stage renal disease, hypertension is extremely common, affecting 86%³⁹ of hemodialysis patients and 80% to 90% of patients following transplantation.⁴⁰ In humans, increased vascular stiffness associated with CAD can contribute to hypertension, which is a known risk factor for left ventricular dilation, ventricular hypertrophy, ischemic heart disease, congestive heart failure, and death.⁴¹

A systolic murmur was identified in approximately two-thirds of cats in this study, and 17% of those patients had a gallop rhythm. Mitral and tricuspid regurgitation were present in approximately 24% and 22% of cats, respectively, at presentation on echocardiographic examination. Hypervolemia resulting from end-stage renal disease can result in valvular regurgitation in this patient population. Other abnormalities identified on echocardiographic examination were common in our study. In addition to myocardial hypertrophy of the IVSd and the LVPWd as well as increases in the LAD and LAD:AoD ratio, both decreases and increases of LVID during diastole and systole were identified. Fractional shortening was abnormal in approximately 28% of cats with 10% having a decrease in FS and approximately 18% having an increase in FS. For humans diagnosed with end-stage renal disease, similar echocardiographic changes associated with uremic CM can result in both diastolic and systolic dysfunction.^4,42,43 While diastolic dysfunction is common in uremic patients and often identified early in the disease progression with preservation of systolic dysfunction,^42,44 the development of systolic dysfunction in human patients is associated with a higher mortality.⁴² Although it is well documented in humans that uremic toxins can cause injury to cardiac myocytes and contribute to the development of CM, there was no significant correlation between uremia and echocardiographic parameters in our study except for a very weak positive correlation between creatinine and IVSd, causing us to reject our first hypothesis. A weak correlation was also identified between PCV and LVIDd. For all cats, there was no significant correlation of echocardiographic parameters and survival to discharge or long-term survival. We accepted our second hypothesis that the presence of echocardiographic changes would not be associated with decreased survival following surgery, which supported our clinical experience working with these patients. It is unclear whether volume depletion associated with end-stage renal disease contributed to any of the changes identified on echocardiography. In a study⁴⁵ performed in healthy cats, volume depletion resulted in an increase in IVSd and LVPWd and a decrease in LVIDd.

In the present study, age was the only variable independently associated with survival following discharge. Cats > 8 years of age were more likely to die at any time following transplantation with a median survival time of 520 days compared to a median survival of 982 days for cats < 8 years of age. These results support previous studies that have identified recipient age as a factor associated with survival following discharge.^1,17,46 In 1 previous report,¹⁷ cats older than 10 years of age had greater mortality rates, particularly during the first 6 months after surgery. In a second report,¹ cats > 12 years of age had a lower overall survival rate compared to younger cats, and a third study⁴⁶ found that median survival times decreased with increasing age, with times of 1,423, 613, and 150 days, respectively, reported for cats younger than 5 years of age, between the ages of 5 and 10 years, and older than 10 years of age. A negative correlation between increasing age and survival following transplantation makes intuitive sense, and in our study, once survival was adjusted for age, no other variable, including those involving cardiac remodeling, remained significant.

Some studies^47–49 in human medicine have identified regression of echocardiographic abnormalities and improvement in long-term survival following successful transplantation, while other studies^42,50 have not demonstrated any beneficial effects. In 1 report,⁴² left ventricular hypertrophy decreased from 75% to 52.1% at 1 year following surgery and improvement in ventricular dilatation and systolic dysfunction was identified. Further prospective studies are necessary to determine if improvement in echocardiographic parameters and cardiac function would occur in cats following successful renal transplantation.

In conclusion, the presence of changes on echocardiographic examination during the transplant screening process should not disqualify a cat as a potential renal transplant recipient. Because of the increased incidence of hypertension identified following successful transplantation in cats, careful monitoring and treatment of hypertension are warranted to prevent injury to the allograft and cardiovascular dysfunction in the future.