Feline comorbidities: cardiovascular and kidney diseases

Abstract

Practical relevance:

Cardiovascular and kidney diseases are highly prevalent and frequently coexistent in cats, particularly those of advanced age. Several pathways of interaction between the heart and kidneys likely contribute to progressive functional decline of these systems during disease of one or both. Identification of heart or kidney disease in a cat should prompt the clinician to consider how the disease and its treatment might impact the function of the other organ and how coexisting primary disease of the other might impact case management and patient prognosis.

Clinical challenges:

A common goal in the management of congestive heart failure, acute kidney injury or chronic kidney disease is to maintain optimal body fluid balance; however, many therapies for disease of one system are at odds with the best interests of the other. For example, treatment of kidney disease often includes parenteral fluid therapy with the goal of maintaining mean arterial pressure and adequate renal blood flow, while diuretics are almost always necessary to reduce capillary hydrostatic pressure in cats with heart failure. Overly aggressive volume expansion or reduction during the management of kidney or heart failure, respectively, can lead to injury to or excessive stress on the other organ system.

Evidence base:

Recommendations are based on available peer-reviewed literature and expert consensus guidelines when available.

Audience:

This article is aimed at all veterinary practitioners who work with cats.

Keywords

Feline cardiomyopathy cardiovascular–renal syndromes cardiorenal syndrome renocardiac syndrome

Introduction

Heart disease is common in domestic cats. The most frequently diagnosed of these diseases – idiopathic primary hypertrophic cardiomyopathy (HCM) – affects 15–16% of apparently healthy cats^1,2 and results in cardiovascular death in 28% of cases.³ In one large study of cats presented to primary care practices in the UK, cardiac disease was the attributed cause of death in 4.6% of those aged 5 years or older.⁴

Kidney disease is also one of the most common causes of morbidity and mortality in cats, particularly those of advanced age. The reported prevalence of chronic kidney disease (CKD) in cats depends on the population studied and diagnostic criteria used, ranging from 2–50% in cats of all ages^5,6 and up to 80% in cats aged 15 years or more.⁵ In the large UK study referenced above, ‘renal disorder’ was the most common cause of death in cats aged 5 years or older, cited in 13.6%.⁴ In addition, cats with kidney disease are frequently diagnosed with systemic arterial hypertension, which has important pathophysiologic consequences for both the kidneys and the heart.

Given the relatively high prevalence of heart and kidney diseases in cats, the intimate relationship between these systems in health and disease, and the fact that disease (or treatment) of one can cause direct or indirect injury or dysfunction of the other, it is unsurprising that clinicians commonly encounter cats with cardiovascular and renal comorbidities. Indeed, in a recent study, 51 (44%) of 116 cats treated for congestive heart failure (CHF) were azotemic prior to initiation of parenteral diuretics.⁷ Likewise, ‘cardiovascular events’ were recorded in 104 (62%) of 168 cats admitted at a different institution for urinary tract obstruction.⁸

In this article, we review the relationships between diseases of the heart and kidneys and present some considerations for the management of cats affected by both.

The cardiorenal axis and cardiovascular–renal disorders

The functions of the heart, blood vessels and kidneys are highly interrelated. Consideration of an integrated ‘cardiorenal axis’ is a useful lens through which to view these complex relationships. As defined by the veterinary Cardiovascular–Renal Axis Disorders Consensus Group, cardiovascular–renal disorders of dogs and cats are ‘disease, toxin or drug-induced structural and/or functional damage to the kidney and/or cardiovascular system, leading to disruption of the normal interaction between these systems, to the ongoing detriment of one or both’.⁹ This approach encourages clinicians to consider connections between the cardiovascular system and kidneys during disease of either or both, and their interactions with other disease conditions. Further, it emphasizes the pathways, often bidirectional, by which disease progression in either or both might be mediated.

Although little is known regarding whether and how frequently primary disease of the kidneys or heart can initiate disease in the other organ, several pathways of interaction between the heart and kidneys likely contribute to progressive functional decline during disease of one or both (Figure 1).

Figure 1

Proposed hemodynamic, neurohormonal and inflammatory pathways linking the heart and kidneys during injury or dysfunction of either. GFR = glomerular filtration rate; RAAS = renin–angiotensin–aldosterone system; RBF = renal blood flow; SNS = sympathetic nervous system. Created in BioRender. Lourenço, B. (2025) https://BioRender.com/z0jijvq

How might heart disease and failure, or the treatment of these, impact kidney function?

Cats with severe heart disease can experience reductions in cardiac output and are at risk of developing systemic arterial hypotension, CHF and arterial thromboembolic complications.

RAAS and SNS activation

While initially compensatory and supportive of glomerular filtration rate (GFR), activation of the renin–angiotensin–aldosterone system (RAAS) and sympathetic nervous system (SNS) leads to chronic myocardial and kidney stress.¹⁰ Heart failure can be viewed as an inflammatory condition,^11–13 with the production of reactive oxygen species and pro-inflammatory mediators leading to endothelial dysfunction and tissue fibrosis. These effects can impair renal blood flow, oxygen delivery and GFR; damage corticomedullary renal tubular cells; and promote renal interstitial inflammation and fibrosis, both part of a final common pathway of disease progression in CKD.¹⁴ In human patients with severe heart disease, the major pathophysiologic role of renal venous congestion and increased intra-abdominal pressure in kidney injury is also well recognized;^15,16 whether this is a factor in cats is currently unstudied. Finally, the pattern (eg, whether sustained, low-level insults or more severe, episodic injuries are to blame) and time course (eg, at which point in the course of cardiac disease or its treatment) of the above effects on the kidney are unclear.¹⁷

Arterial thromboembolism leading to renal infarction

Cats with heart disease frequently experience arterial thromboembolism (ATE).³ While this most commonly manifests as distal aortic thromboembolism (ie, ‘saddle thrombus’), the kidneys can also be a direct target.¹⁸ The prevalence of renal artery thromboembolism in cats with heart disease is undetermined. However, cats with renal infarction (Figure 2) appear more likely to have echocardiographic evidence of heart disease than those without.^19,20

Figure 2

Two-dimensional transabdominal ultrasound image taken in a sagittal plane through the right kidney of a cat with chronic kidney disease. There are undulant cortical margins, wedge-shaped hyperechoic renal cortical infarcts (RI) and a diffuse decrease in corticomedullary distinction

Pharmacologic agents used for cardiovascular disease and heart failure

Drugs commonly used to treat heart disease and failure (eg, loop diuretics, angiotensinconverting enzyme inhibitors [ACEis]) or systemic arterial hypertension (eg, angiotensin receptor blockers [ARBs]) can affect kidney perfusion, renal autoregulation and glomerular hemodynamics, particularly when administered at high dosages alone or in combination, or when given in the setting of decreased circulating blood volume.^21–23 While they represent a cornerstone of therapy for both acute and chronic life-threatening CHF in cats,^24,25 loop diuretics can impair renal autoregulation and reduce renal blood flow under certain conditions by interfering with tubuloglomerular feedback.^22,26

How common is kidney injury in cats with primary heart disease?

Azotemia is common in cats with apparently asymptomatic cardiomyopathy²⁷ and in those with acute CHF even before CHF has been treated.^7,12,27,28 Serum creatinine concentrations >2.1 mg/dl (186 µmol/l) or >1.6 mg/dl 140 µmol/l) were documented prior to furosemide therapy in 11 (24%) of 45 cats²⁸ and 51 (44%) of 116 cats⁷ hospitalized for acute CHF, respectively. In the larger of these studies, only 21 (18%) of 116 cats had known CKD at intake, suggesting that kidney injury due to primary heart disease might have explained pretreatment azotemia in some of the cases, although interpretation is complicated by the cats’ advanced age (median [range], 10 years [0.8–19.3]) and challenges in diagnosing early-stage CKD. In the same study, 75% of cats experienced a serum creatinine concentration >1.6 mg/dl (140 µmol/l) at some point during hospitalization, and the frequency of serum creatinine concentration >1.6 mg/dl remained high (ie, 45–69% of surveilled cases) post-discharge.⁷ Increases ⩾0.3 mg/dl in serum creatinine concentration, consistent with the study’s definition of kidney injury, were experienced by 49% of cats during hospitalization,⁷ in keeping with previous studies.^28,29 While, in general, acute increases in serum creatinine have been linked to worse outcomes in cats,³⁰ kidney injury (as defined above) coincident with acute CHF treatment was not associated with poorer long-term prognosis in the study performed by Rogg and colleagues.⁷

How might kidney disease and its treatment impact cardiovascular function?

The kidney regulates extracellular fluid volume and composition (including electrolyte concentrations) and systemic arterial blood pressure (BP). Due to renal functional derangements or drugs and therapies used in their treatment, cats with kidney disease can experience excesses or deficits of blood volume and pressure that affect cardiovascular function. Aside from the established effects of systemic arterial hypertension on the heart, whether these other derangements can induce heart disease or failure de novo is unclear; however, for cats with underlying heart disease, they are likely relevant.

Hypo- and hypervolemia

Uremic cats can experience hypovolemia due to obligatory polyuria if not met by sufficient intake, or fluid losses associated with vomiting or diarrhea, leading to decreases in cardiac output. Conversely, kidney disease can be associated with hypervolemia due to aggressive parenteral fluid administration, abnormal renal sodium and water handling, activation of the RAAS and chronic anemia, all of which can exacerbate heart disease and failure by increasing the workload of the heart.

Cats with kidney disease frequently require parenteral fluid therapy to address excessive renal and (when uremic) gastrointestinal fluid losses. While supplemental fluids can restore euvolemia and euhydration, their use – particularly of sodium-rich, isotonic crystalloids – can promote excessive extracellular fluid volume if not carefully optimized to patient needs.³¹ This can be particularly problematic when administration is for long periods or at high rates to cats with underlying heart disease. Similarly, blood transfusion for severe anemia can cause transfusion-associated circulatory overload.³²

Systemic arterial hypertension

Systemic arterial hypertension is noted in 40–61% of cats with CKD^33,34 and 28% of those with acute kidney injury (AKI).³⁵ It is the most well established pathophysiologic connection between kidney and heart diseases. The relationship between kidney disease and systemic arterial hypertension,³⁶ and the importance of the heart, vasculature and kidneys as targets of hypertensive end-organ damage, are detailed elsewhere.^37,38 In small cross-sectional studies, 48–85% of systemically hypertensive cats have echocardiographic evidence of hypertensive cardiomyopathy (Figure 3).^39–42 However, the clinical relevance of these changes is unclear. Although a cardiovascular cause of death or complication at the time of euthanasia was assigned for 4 (21%) of 19 hypertensive cats who died in one study,⁴³ the authors of a separate report found no significant difference in mean survival time between hypertensive cats with or without echocardiographic abnormali-ties.³⁹ It is uncommon for a cat to develop CHF or arterial thromboembolism secondarily to systemic arterial hypertension alone.⁴⁴ However, its consequences are relevant in patients with pre-existing heart disease or those undergoing additional hemodynamic stressors (eg, blood transfusion, intravenous fluid therapy), in whom CHF might be more easily precipitated.

Figure 3

Two-dimensional (a) long- and (b) short-axis transthoracic echocardiographic images taken from a 10-year-old spayed female cat with chronic kidney disease and untreated systemic arterial hypertension (average indirect systolic blood pressure, 200 mmHg). Each image was taken at end-diastole from a right parasternal view. There is moderate-to-severe concentric hypertrophy of the left ventricular wall. IVS = interventricular septum; LA = left atrium; LV = left ventricle; LVFW = left ventricular free wall

Electrolyte derangements

Kidney disorders are frequently accompanied by electrolyte derangements. These include hypo- and hyperkalemia, hypo-and hypercalcemia, and hyperphosphatemia, which are common in cats with AKI^45–48 or CKD^45,49–51 and can affect cardiovascular function and structure.

Potassium abnormalities can alter cardiac excitability and lead to brady- or tachyarrhythmias (eg, sinus bradycardia, transient atrial standstill, sinoventricular rhythm, ventricular tachyarrhythmias, asystole)^52,53 or abnormalities of cardiac conduction (Figure 4). In one retrospective study of 96 azotemic cats with acute ureteral or urethral obstruction, hyperkalemia was reported in 45 (46%) and serum potassium concentration was significantly associated with the occurrence of cardiovascular events – 34% of which were arrhythmias – based on multivariate analysis.⁸ Conversely, hypokalemia is more common with polyuria and is therefore most likely in cats with CKD who are not fed a potassium-supplemented therapeutic renal diet,⁴⁹ especially those with mild or moderate decreases in GFR (ie, International Renal Interest Society [IRIS] CKD stages 2 or 3) or those with diuresis following relief of urethral obstruction.⁵⁴

Figure 4

Lead II surface electrocardiograms (paper speed, 50 mm/s; sensitivity, 20 mm/mV) taken (a) before and (b) after treatment of severe hyperkalemia (serum potassium concentration, 8.18 mmol/l [reference interval (RI), 3.41–4.76]) in a 7-year-old castrated male cat with aortic and renal arterial thromboembolism. In both recordings, the rhythm is sinus. After treatment, there is normalization of P wave amplitude (0.05–0.2 mV), PR interval (0.10–0.07 s [RI, 0.05–0.09]), QRS duration (0.07–0.03 s [RI <0.04 s]) and T wave morphology and amplitude (RI ± 0.3 mV)

Calcium is critical for normal cardiomyocyte contraction, cardiac automaticity and nodal conduction, and excitation–contraction coupling.^55,56 In humans, low blood calcium concentrations can cause systemic arterial hypotension due to clinically relevant compromises in myocardial and vascular smooth muscle contract-ility.^57,58 Conversely, sustained hypercalcemia, which can occur in CKD– mineral and bone disorder (CKD– MBD), can promote vascular mineralization and is associated with increased cardiovascular morbidity and mortality in people.^59–62 Although vascular mineralization is recognized in cats with CKD,^63,64 the impact of calcium disorders on cardiovascular outcomes remains understudied.

Finally, decreased renal excretion of phosphate stimulates the production of fibroblast growth factor 23 (FGF-23), which is central to the pathophysiology of CKD–MBD.⁶⁵ Increased circulating phosphate and FGF-23 concentrations are important risk factors for CKD progression and mortality in cats,^66–68 and strongly predict worse cardiovascular outcomes in humans, likely due in part to the dystrophic mineralization they promote.^69–71

CKD-associated anemia

The anemia of CKD increases in prevalence and severity with disease stage.⁵⁰ In addition to exacerbating renal hypoxia and oxidative stress and accelerating CKD progression in cats,⁷² chronic anemia triggers detrimental adaptations (eg, RAAS and SNS activation) that expand extracellular fluid volume, increase cardiac workload, and promote left ventricular and left atrial hypertrophy.⁷³ These effects can be clinically relevant (Figure 5): in one report of eight severely anemic (ie, hematocrit ⩽18%) cats without underlying heart disease or systemic arterial hypertension, left heart enlargement and CHF were noted in 100% and 71%, respectively.⁷⁴ While these data are almost certainly influenced by selection bias – included cats had to have undergone echocardiography – they illustrate the potentially serious cardiovascular consequences of anemia.

Figure 5

(a) Left lateral and (b) ventrodorsal thoracic radiographs taken from a 10-year-old spayed female cat with chronic kidney disease (International Renal Interest Society stage 3, normotensive) and chronic non-regenerative anemia (packed cell volume, 25%), receiving once daily treatment with subcutaneous fluids. There is mild-to-moderate cardiomegaly, a mild amount of pleural effusion and a multifocal interstitial coalescing-to-patchy alveolar pulmonary pattern, consistent with congestive heart failure

Erythropoiesis-stimulating agents (eg, dar-bepoetin) are used in cats with declining quality of life due to CKD-associated ane-mia,⁷⁵ potentially benefitting the kidneys and heart in addition to improving clinical signs. However, systemic arterial hypertension is a well-known potential adverse effect of this drug class,^76,77 so careful monitoring of BP is recommended during therapy. Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates endogenous production of erythropoietin, and for which currently available data do not support an effect on BP in cats,⁷⁸ might represent a potentially viable alternative for this indication. At the time of writing, molidustat has conditional approval in the USA for the treatment of non-regenerative anemia in cats with CKD. However, drugs of the same class are associated with the development of systemic arterial hypertension in humans,⁷⁹ suggesting that BP monitoring is advisable in treated cats.

RAAS and SNS activation

As in heart disease, excessive activation of the RAAS and SNS occurs in kidney disease independent of anemia (Figure 1). As mentioned above, the chronic hemodynamic (eg, increases in blood volume and pressure) and non-hemodynamic (eg, pro-inflammatory, pro-fibrotic, pro-oxidative stress) effects can harm the kidneys and cardiovascular system.⁸⁰ While evidence for activation of the circulating RAAS in cats with kidney disease is inconsistent, activation of the local, independently regulated, intrarenal RAAS is likely.^81–85

Reduced renal clearance of cardiovascular pharmacologic agents

Abnormal kidney function can reduce the renal clearance of various pharmacologic agents. This is potentially clinically relevant for cardiovascular drugs whose parent compound or active metabolites (eg, atenolol, enalapril and its active metabolite, enalapri-lat) are primarily eliminated by the kidneys (Table 1), as this would raise concerns for drug accumulation and increased risk of dosedependent adverse effects.^86,91 Therefore, dose reductions or the selection of other drugs in the same class with no or less renal elimination might be necessary in cats with kidney function impairment. For example, the clearances of benazepril and benazeprilat, which largely undergo biliary elimination, are unaffected by reduced kidney function in cats.⁹²

Table 1

Mode of endogenous elimination for drugs commonly used in the treatment of cardiovascular disease of cats

Indication	Drug class	Drug	Primary mode(s) of elimination
Arrhythmia or cardiomyopathy	✜ Beta (3)-adrenergic receptor blocker	✜ Atenolol*	✜ Renal excretion (humans)⁸⁶
	✜ Potassium channel- and 3-adrenergic receptor-blocker	✜ Sotalol*	✜ Renal excretion^{87 †}
Congestive heart failure	✜ Loop diuretic	✜ Furosemide*	✜ Renal excretion^{88 †}
		✜ Torsemide	✜ 37% eliminated in urine as unchanged drug^{89 †} ✜ Substantial hepatic elimination (humans)⁹⁰
	✜ Angiotensin-converting enzyme inhibitor	✜ Enalapril*	✜ Renal excretion of the active metabolite, enalaprilat (dogs)⁹¹
		✜ Benazepril	✜ Unpublished data: hepatobiliary excretion (85%)^{92 †} ✜ Biliary (55%) and renal (45%) excretion of the active metabolite, benazeprilat (dogs)⁹¹
	✜ Inodilator	✜ Pimobendan	✜ Hepatobiliary/fecal excretion (dogs)⁹³
		✜ Dobutamine*	✜ Renal (67%) and fecal (20%) excretion (dogs)⁹⁴
Thrombosis prophylaxis	✜ Platelet aggregation inhibitor	✜ Clopidogrel*	✜ Renal (50%) and fecal (46%) excretion (humans)⁹⁵
	✜ Factor Xa inhibitor	✜ Rivaroxaban	✜ Renal excretion of unchanged drug (33%), hepatic metabolism to inactive metabolites (66%; humans)⁹⁶
Systemic arterial hypertension	✜ Angiotensin receptor blocker	✜ Telmisartan	✜ Hepatobiliary/fecal excretion (dogs, humans)⁹⁷ ✜ Glucuronidation⁹⁸⁷
	Calcium channel blocker	Amlodipine*	Hepatobiliary/fecal (40-75%) and renal (25-60%) excretion, depending on the species⁹⁹

Drugs for which greater than half of the dose is eliminated by the kidneys in cats (if data for this species are available) or in at least one other species (if data for cats are not available)

†

Pharmacokinetic data generated in cats are available. In all other instances, information was extrapolated from other species

Suboptimization of heart failure protocols

Finally, there is a general lack of evidence to guide heart failure therapies in cats with advanced kidney disease, which might impact cardiovascular function and outcomes. An easily imagined effect is the underprescription and suboptimization of heart failure protocols – an idea that is supported by experience in human medicine.¹⁰⁰ For example, in one retrospective study of 20,902 elderly patients in heart failure, prescription of ACEis, beta-adrenergic blockers or both, was associated with similar reductions in 1-year mortality risk in patients with and without azotemic CKD (ie, serum creatinine >2.0 mg/dl) compared with patients treated with neither drug.¹⁰¹ However, in that study and anoth-er,¹⁰² these drugs were less often prescribed to patients with azotemic CKD compared with those without.

Recommendations for diagnostic testing in patients with cardiovascular or kidney disease

Identification of heart or kidney disease in a cat should prompt the clinician to consider how the disease and its treatment might impact the function of the other organ and how coexisting primary disease of the other might impact case management and patient prognosis. This might include complete disease staging and screening for other diseases and conditions (eg, hyperthyroidism, systemic arterial hypertension) that might explain or exacerbate disease in one or both systems.

Assessment of kidney function in patients with heart disease

The IRIS classification systems for AKI and CKD⁷⁵ are useful for the characterization and grading (AKI; Table 2) or staging (CKD; Table 3) of kidney function in any patient, including those with heart disease.

Table 2

International Renal Interest Society (IRIS) grading and subgrading criteria for acute kidney injury (AKI)¹⁰⁹

AKI grading
Grade	Blood creatinine
Grade	µmol/l	mg/dl	Clinical description
Grade I	<140	<1.6	Non-azotemic AKI AKI evidenced by the history, presence of oligoanuria (UOP <1 ml/kg/h), clinicopathologic data (eg, SDMA >reference interval, renal glucosuria, cylindruria, renal proteinuria, inflammatory sediment, microalbuminuria) or urinary tract imaging Includes cats with: – Progressive, non-azotemic increases in blood Cr ⩾26.4 µmol/l (⩾0.3 mg/dl) over 48 h – Volume-responsive AKI (ie, UOP >1 ml/kg/h within 6 h; decrease in Cr to baseline within 48 h)
Grade II	140*–220	1.6*–2.5	Mild AKI: Documented AKI (as defined for grade I) with mild azotemia Includes cats with: – Progressive, azotemic increases in blood Cr ⩾26.4 µmol/l (⩾0.3 mg/dl) over 48 h – Volume-responsive AKI (as defined for grade I)
Grade III	221–439	2.6–5.0	Moderate to severe AKI:
Grade IV	440–880	5.1–10.0	Documented AKI (as defined for grade I) with progressively greater degrees of parenchymal damage and functional failure (uremia)
Grade V	>880	>10.0
AKI subgrading
Characteristic			Clinical description
UOP	Non-oliguric		UOP >1 ml/kg/h
	Oligoanuric		UOP <1 ml/kg/h or anuria (ie, no urine produced) over 6 h
Need for RRT	Not required		Standard therapy sufficient
	Required		RRT is required to eliminate nephrotoxins or correct life-threatening iatrogenic or clinical consequences of AKI (eg, severe azotemia, hyperkalemia, acid–base disorders, overhydration, oligoanuria)

Lower limits differ from published values (ie, 141 µmol/l and 1.7 mg/dl); changed here after personal communication with an IRIS board member Cr = creatinine; RRT = renal replacement therapy; SDMA = symmetric dimethylarginine; UOP = urine output

Table 3

International Renal Interest Society (IRIS) staging and substaging of chronic kidney disease (CKD) in cats¹⁰⁹

CKD staging
Stage	Blood creatinine		BloodSDMA(µg/dl)	Clinical description
Stage	µmol/l	mg/dl	BloodSDMA(µg/dl)
Stage 1	<140	<1.6	<18	Normal Cr; normal or mildly increased blood SDMA Other renal abnormalities noted (eg, inadequate urinary concentrating ability in the absence of a non-renal cause; abnormal renal palpation or imaging; renal proteinuria; SDMA persistently >14 µg/dl, increasing Cr or SDMA in serial samples; abnormal renal histopathology)
Stage 2	140–250	1.6–2.8	18-25	Normal or mildly increased creatinine, mild renal azotemia Mildly increased SDMA Clinical signs usually absent
Stage 3	251–440	2.9–5.0	26-38	Moderate renal azotemia Extrarenal signs may be present, but their extent and severity may vary
Stage 4	>440	>5.0	>38	Increasing risk of systemic clinical signs and uremic crises
CKD substaging based on proteinuria
UPC			Proteinuria substage
<0.2			Non-proteinuric
0.2–0.4			Borderline proteinuric
>0.4			Proteinuric
CKD substaging based on blood pressure
Systolic BP (mmHg)	Blood pressure substage		Risk of TOD
<140	Normotensive		Minimal
140–159	Prehypertensive		Low
160–179	Hypertensive		Moderate
⩾180	Severely hypertensive		High

BP = blood pressure; Cr = creatinine; SDMA = symmetric dimethylarginine; TOD = target organ damage; UPC = urinary protein:creatinine ratio

Evaluation of routine blood and urinary biomarkers – including markers of GFR (ie, serum creatinine, symmetric dimethylarginine [SDMA] and urea nitrogen concentrations), serum electrolyte and albumin concentrations, urine specific gravity, urinary protein:creatinine ratio, and presence of renal glucosuria or cylindruria – allows the clinician to screen for kidney injury with reasonable sensitivity. However, functional markers like serum creatinine and SDMA concentrations are poorly sensitive and specific for mild injury characterized by little (or current) impact on glomerular filtration. Furthermore, the influences of heart function and medications for cardiovascular disease on renal blood flow and GFR can substantially impact the utility of these markers to diagnose intrinsic kidney disease in cats with concurrent heart disease (Table 4). Repeated sampling and documentation of progressive increases in serum creatinine or SDMA concentrations within the normal reference interval are likely to increase the sensitivity of these markers for the detection of decreased kidney function.

Table 4

Potential impacts of kidney or heart dysfunction on tests used to monitor or diagnose disease of the other organ

Diagnostics used for assessment of kidney function or disease
Test	Assesses	Considerations in patients with heart dysfunction
Creatinine BUN SDMA	GFR	✜ GFR is impacted by cardiac output and renal perfusion ✜ Circulating concentrations can be increased (signaling decreased GFR) in cats with heart failure, even in the absence of intrinsic renal disease
Urine output	Glomerular filtration and tubular function	✜ Filtration and tubular function are impacted by cardiac output and renal perfusion ✜ Urine output can be decreased in cats with heart failure
Diagnostics used for assessment of heart function or disease
Test	Assesses	Considerations in patients with kidney dysfunction
Cardiac auscultation	Heart sounds	✜ Heart murmurs or gallop sounds can be caused by chronic CKD-associated anemia or systemic arterial hypertension alone ✜ Electrolyte derangements can cause cardiac arrhythmias even in the absence of primary cardiac disease
NT-proBNP	Cardiac stretch or stress	✜ These markers undergo renal clearance
Cardiac troponin I	Cardiomyocyte damage	✜ Circulating concentrations can be increased in cats with kidney dysfunction, even in the absence of primary cardiac disease
Echocardiography	Cardiac structure and function	Even in the absence of primary heart disease: ✜ Hypovolemia from urinary fluid losses can reduce cardiac chamber size and lead to concentric ‘pseudohypertrophy’ of the ventricular walls, mimicking an HCM phenotype ✜ Chronic CKD-associated anemia can cause cardiac chamber dilatation ✜ Chronic CKD-associated systemic arterial hypertension can cause concentric left ventricular hypertrophy (HCM phenotype)
Thoracic radiography	Cardiac size and whether CHF is likely present	✜ Hypovolemia from urinary fluid losses can reduce heart size ✜ Chronic CKD-associated anemia can cause or exacerbate cardiomegaly or heart failure ✜ Chronic CKD-associated systemic arterial hypertension can cause (if severe and long-standing) or exacerbate cardiomegaly or heart failure

BUN = blood urea nitrogen; CKD = chronic kidney disease; CHF = congestive heart failure; GFR = glomerular filtration rate; HCM = hypertrophic cardiomyopathy; NT-proBNP = N-terminal prohormone of B-type natriuretic peptide; SDMA = symmetric dimethylarginine

For cats with heart disease whose treatment includes a diuretic, it can be challenging to differentiate among volume-responsive (previously, ‘prerenal’) azotemia, azotemia due to acute kidney injury and chronic cardiovascular disease leading to progressive CKD (ie, type 2 cardiovascular–renal syndrome). Importantly, because of the urine-diluting effects of diuretics, urine specific gravity measurements cannot be used to help determine whether azotemia is most likely due to extrarenal causes. Ultrasonographic changes to the kidneys (see below), senior or geriatric patient age, and the presence of non-regenerative anemia increase concern for intrinsic renal azotemia. There is growing interest in the use of urinary biomarkers of kidney injury (eg, urinary cystatin B, clusterin, neutrophil gelatinase-associated lipocalin) to detect early or active/ongoing damage.^111–114 Of these, only a test for urinary cystatin B is commercially available at the time of writing. The effects of extrarenal conditions, including heart and vascular diseases, on these markers deserve future study.

In cats with heart disease, radiographic or ultrasonographic evaluation of kidney structure can be useful to diagnose concurrent kidney disease. Imaging should be considered for cats whose kidney health status is questioned but unclear based on clinicopathologic findings. Small, irregularly shaped kidneys, greater than normal echogenicity of the renal cortex and medulla, decreased cortico-medullary distinction, loss of normal internal architecture or a combination of these supports a diagnosis of CKD.^115,116 An intrinsic acute nephropathy is suggested by enlarged kidneys and increased cortical echogenicity with preserved corticomedullary distinction, whereas marked pyelectasia or hydronephrosis, hydroureter or ureteral calculi can signal obstructive nephropathy.^115,116

Assessment of cardiac structure and function in cats with kidney disease

Imaging of the cardiopulmonary structures is necessary for accurate and comprehensive assessment of heart structure and function, and is recommended for cats with kidney disease who also have historical or clinical findings suggestive of heart disease or failure. The American College of Veterinary Internal Medicine feline cardiomyopathy staging system can be used to characterize the clinical impact of cardiomyopathy in cats (Table 5).²⁵

Table 5

American College of Veterinary Internal Medicine staging of feline cardiomyopathy²⁵

Stage		Clinical description
A	Predisposed	✜ Cats predisposed to cardiomyopathy without evidence of myocardial disease
B1	Subclinical (low risk)	✜ Cats with cardiomyopathy but without clinical signs✜ Normal atrial size or mild atrial enlargement ✜ Low risk of imminent CHF or ATE
B2	Subclinical (high risk)	✜ Cats with cardiomyopathy but without clinical signs ✜ Moderate or severe atrial enlargement ✜ Higher risk of imminent CHF or ATE ✜ Additional risk factors for CHF or ATE: presence of gallop sound or arrhythmia; decreased left atrial function; extreme left ventricular hypertrophy; left ventricular systolic dysfunction; spontaneous echogenic contrast or thrombus; regional wall motion abnormalities
C	Current or previous CHF or ATE	✜ Cats who have developed signs of CHF or ATE, even if these resolve with treatment
D	Refractory CHF	✜ Cats with signs of CHF refractory to high oral dosages (>6 mg/kg/day) of furosemide

ATE =arterial thromboembolism; CHF = congestive heart failure

In an ideal world, and assuming no practical or financial limitations, all cats with known kidney disease would undergo assessment of cardiac structure and function using complementary information from echocardiography and thoracic radiography. This is because in this species, physical examination findings (eg, presence of a heart murmur or gallop) and thoracic radiography alone have poor sensitivity for the identification of subclinical heart disease and heart enlargement, respectively.^1,117,118 Instead, the clinical gold standard for assessment of cardiac structure and function is echocardiography, which allows for the diagnosis, specific phenotyping and staging of heart disease. The findings of thoracic radiography complement echocardiographic data by determining whether signs of CHF are present.

Echocardiography is not feasible in all cases or for all owners, however. The most practical reason to screen for heart disease in cats with kidney disease is to identify individuals who, compared with cats without heart disease, are at meaningfully increased risk for complications (eg, CHF, ATE, cardiac arrhythmias) when challenged with certain interventions or stressors. This largely equates to cats with moderate or severe heart disease/injury and enlargement.¹¹⁹

The accuracy of widely available circulating cardiac biomarker (eg, N-terminal prohormone B-type natriuretic peptide [NT-proBNP], cardiac troponin I) concentrations to establish the presence of subclinical heart disease or injury in cats with kidney disease is limited by several factors. Among the most relevant is that both biomarkers undergo renal clearance, which decreases their specificity for cardiac injury in cats with abnormal kidney function (Table 4).^120,121 In addition, little is known about their performance compared with echocardiography in cats with AKI or CKD. Therefore, the use of cardiac biomarker concentrations in isolation to rule in heart disease or injury in this situation is not advised. However, NT-proBNP concentration might be a useful component of screening protocols in certain cases, as discussed below.¹²²

In the authors’ practice, echocardiography is most strongly recommended for cats with kidney disease who have one or more of the following, particularly when treatments (ie, parenteral fluids, blood transfusion) that increase the workload of the heart are planned: (1) historical or clinical findings suggestive of current or previous heart disease or failure; (2) thoracic radiographic findings suggestive of cardiomegaly, cardiogenic edema or effusions, or both; or (3) physical examination findings that, when present, imply increased risk of cardiomyopathy (eg, loud [⩾grade IV/VI] heart murmur, gallop sound or arrhythmia).^25,119 The information provided can allow for the formulation of a rational treatment plan that minimizes the risk of excess hemodynamic stressors on a diseased heart. This approach is supported by the findings of one study in which 61 (51%) of 120 cats with CHF experienced antecedent events (eg, intravenous fluid administration, anesthesia, surgery, corticosteroid administration) that might have precipitated the episode.¹²³

In cats for whom echocardiography is not feasible, the combined results of serum NT-proBNP concentrations and thoracic radiographs can help to identify cases that are unlikely to have moderate or severe heart disease or failure. Importantly, this approach will misclassify some cats with mild forms of disease (false negative) or normal hearts (false positive), although ‘clinically relevant’ disease is less likely in older cats with normal findings in both tests.¹²⁴ However, this approach has not been rigorously tested in cats with kidney disease.

Assessment of systemic arterial BP in cats with heart or kidney disease

Given the link between BP abnormalities and heart and kidney disease, the authors, as well as a consensus panel of veterinary cardiologists and nephrologists,⁹ recommend routine monitoring of systemic arterial BP in cats with diseased kidneys, with the goal of identifying and correcting pathologic systemic arterial hypertension or hypotension. In the authors’ practice, routine BP monitoring is also performed in cats with moderate or severe heart disease who have risk factors for systemic hypertension, clinical signs of CHF or are receiving medications known to impact systemic BP.

Considerations for the management of patients with concurrent cardiovascular and renal diseases

A common goal in the management of CHF, AKI or CKD is to achieve and maintain optimal body fluid balance. However, many therapies for disease of one system are fundamentally at odds with the best interest of the other. For example, the treatment of kidney disease often includes parenteral fluid therapy with the goal of maintaining mean arterial pressure and adequate renal blood flow, while diuretics are almost always necessary to reduce capillary hydrostatic pressure in cats with CHF. Overly aggressive volume expansion or reduction during the management of kidney or heart failure, respectively, can lead to injury to or excessive stress on the other system. Two commonly encountered clinical scenarios are described on the following pages to illustrate the balance required to manage cats with concurrent underlying disease of both systems. In general, the approach should be to treat the system whose decompensation is responsible for the patient’s clinical signs in a manner that minimizes risk to the other system and the cardiovascular–renal axis.

Key Points

✜ Heart and kidney diseases frequently coexist in the same cat.

There are several pathways of interaction between the heart and kidneys during health and disease, and it is helpful to think of these systems as belonging to an integrated ‘cardiovascular–renal axis’.

✜ One of the most well-described links between heart and kidney diseases is systemic arterial hypertension, which is frequently associated with CKD in cats, and can lead to progressive damage to both. Given the link between BP abnormalities and heart and kidney diseases, routine monitoring of systemic arterial BP and the use of antihypertensive therapy (eg, amlodipine, telmisartan) in cats with diseased kidneys is recommended.

✜ The general approach to the treatment of cats with both conditions should be to treat the system whose decompensation is responsible for the patient’s clinical signs in a manner that minimizes risk to the other system and the cardiovascular–renal axis.

Footnotes

Conflict of interest

Amanda Coleman declares no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Bianca Lourenço has received research funding, speaker honoraria, and consulting fees from Ceva Animal Health and Boehringer Ingelheim Vetmedica, and research funding from Elanco Animal Health.

Funding

The authors of this commissioned Clinical Spotlight review received an honorarium; as for all JFMS articles, this Clinical Spotlight article went through peer review.

Ethical approval

This work did not involve the use of animals and therefore ethical approval was not specifically required for publication in JFMS.

Informed consent

This work did not involve the use of animals (including cadavers) and therefore informed consent was not required. No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Amanda E Coleman

Bianca N Lourenço

References

Paige

Abbott

Elvinger

et al. Prevalence of cardiomyopathy in apparently healthy cats. J Am Vet Med Assoc 2009; 234: 1398–1403.

Payne

Brodbelt

Luis Fuentes

Cardiomyopathy prevalence in 780 apparently healthy cats in rehoming centres (the CatScan study). J Vet Cardiol 2015; 17 Suppl 1: 244–257.

Fox

Keene

Lamb

et al. International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: the REVEAL study. J Vet Intern Med 2018; 32: 930–943.

O’Neill

Church

McGreevy

et al. Longevity and mortality of cats attending primary care veterinary practices in England. J Feline Med Surg 2015; 17: 125–133.

Marino

Lascelles

Vaden

et al. Prevalence and classification of chronic kidney disease in cats randomly selected from four age groups and in cats recruited for degenerative joint disease studies. J Feline Med Surg 2014; 16: 465–472.

O’Neill

Church

McGreevy

et al. Prevalence of disorders recorded in cats attending primary-care veterinary practices in England. Vet J 2014; 202: 286–291.

Rogg

Mochel

Kundu

et al. Frequency and progression of azotemia during acute and chronic treatment of congestive heart failure in cats. J Vet Intern Med 2025; 39. DOI: 10.1111/jvim.17254.

Duperrier-Simond

Pouzot-Nevoret

Allaouchiche

et al. Occurrence of cardiovascular events in 168 cats with acute urinary tract obstruction. Can Vet J 2024; 65: 67–74.

Pouchelon

Atkins

Bussadori

et al. Cardiovascular–renal axis disorders in the domestic dog and cat: a veterinary consensus statement. J Small Anim Pract 2015; 56: 537–552.

10.

Adams

Jr.

Pathophysiologic role of the renin–angiotensin–aldosterone and sympathetic nervous systems in heart failure. Am J Health Syst Pharm 2004; 61 Suppl 2: 4–13.

11.

Mohebi

Liu

van Kimmenade

et al. Inflammation across universal definition of heart failure stages: the CASABLANCA study. Eur J Heart Fail 2023; 25: 152–160.

12.

Liu

Köster

Fosgate

et al. Cardiovascular–renal axis disorder and acutephase proteins in cats with congestive heart failure caused by primary cardiomyopathy. J Vet Intern Med 2020; 34: 1078–1090.

13.

Homilius

Achilles

et al. Metabolic abnormalities and reprogramming in cats with naturally occurring hypertrophic cardiomyopathy. ESC Heart Failure 2025; 12: 1256–1270.

14.

Mimura

Nangaku

The suffocating kidney: tubulointerstitial hypoxia in endstage renal disease. Nat Rev Nephrol 2010; 6: 667–678.

15.

Dupont

Mullens

Tang

WH.

Impact of systemic venous congestion in heart failure. Curr Heart Fail Rep 2011; 8: 233–241.

16.

Rangaswami

Mechanistic insights in cardiorenal syndrome. NEJM Evid 2022; 1. DOI: 10.1056/EVIDra2200053.

17.

Cowgill

Polzin

Elliott

et al. Is progressive chronic kidney disease a slow acute kidney injury? Vet Clin North Am Small Anim Pract 2016; 46: 995–1013.

18.

Smith

Tobias

Jacob

et al. Arterial thromboembolism in cats: acute crisis in 127 cases (1992–2001) and long-term management with low-dose aspirin in 24 cases. J Vet Intern Med/ACVIM 2003; 17: 73–83.

19.

Gibson

Lourenco

De la Rosa

et al. Diagnostic value of echocardiography in cats with and without ultrasonographic evidence of renal infarction. J Vet Intern Med 2025; 39. DOI: 10.1111/jvim.70107.

20.

Hickey

Jandrey

Farrell

et al. Concurrent diseases and conditions in cats with renal infarcts. J Vet Intern Med 2014; 28: 319–323.

21.

Lee

Baek

Lee

et al. Retrospective evaluation of risk factors for worsening renal function after angiotensin-converting enzyme inhibitor treatment in dogs. J Vet Intern Med 2025; 39. DOI: 10.1111/jvim.17252.

22.

Duchin

Peterson

Burke

TJ.

Effect of furosemide on renal autoregulation. Kidney Int 1977; 12: 379–386.

23.

Kaloyanides

Bastron

DiBona

GF.

Impaired autoregulation of blood flow and glomerular filtration rate in the isolated dog kidney depleted of renin. Circ Res 1974; 35: 400–412.

24.

Rishniw

Pion

PD.

Is treatment of feline hypertrophic cardiomyopathy based in science or faith? A survey of cardiologists and a literature search. J Feline Med Surg 2011; 13: 487–497.

25.

Luis Fuentes

Abbott

Chetboul

et al. ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats. J Vet Intern Med 2020; 34: 1062–1077.

26.

Just

Wittmann

Ehmke

et al. Autoregulation of renal blood flow in the conscious dog and the contribution of the tubu-loglomerular feedback. J Physiol 1998; 506 (Pt 1): 275–290.

27.

Gouni

Chetboul

Pouchelon

et al. Azotemia in cats with feline hypertrophic cardiomyopathy: prevalence and relationships with echocardiographic variables. J Vet Cardiol 2008; 10: 117–123.

28.

Goutal

Keir

Kenney

et al. Evaluation of acute congestive heart failure in dogs and cats: 145 cases (2007–2008). J Vet Emerg Crit Care (San Antonio) 2010; 20: 330–337.

29.

Ohad

Segev

Kelmer

et al. Constant rate infusion vs. intermittent bolus administration of IV furosemide in 100 pets with acute left-sided congestive heart failure: a retrospective study. Vet J 2018; 238: 70–75.

30.

Harison

Langston

Palma

et al. Acute azotemia as a predictor of mortality in dogs and cats. J Vet Intern Med 2012; 26: 1093–1098.

31.

Langston

Gordon

Effects of IV fluids in dogs and cats with kidney failure. Front Vet Sci 2021; 8: DOI: 10.3389/fvets.2021.659960.

32.

Taylor

Spada

Callan

et al. 2021 ISFM consensus guidelines on the collection and administration of blood and blood products in cats. J Feline Med Surg 2021; 23: 410–432.

33.

Bijsmans

Jepson

Chang

et al. Changes in systolic blood pressure over time in healthy cats and cats with chronic kidney disease. J Vet Intern Med 2015; 29: 855–861.

34.

Kobayashi

Peterson

Graves

et al. Hypertension in cats with chronic renal failure or hyperthyroidism. J Vet Intern Med 1990; 4: 58–62.

35.

Cole

Jepson

Humm

Systemic hypertension in cats with acute kidney injury. J Small Anim Pract 2017; 58: 577–581.

36.

Lawson

Jepson

RE.

Feline comorbidities: the intermingled relationship between chronic kidney disease and hypertension. J Feline Med Surg 2021; 23: 812–822.

37.

Coleman

Brown

SA.

Hypertension and the heart and vasculature. In: Elliott

Syme

Jepson

(eds). Hypertension in the dog and cat. Springer, 2020, pp 187–215.

38.

Elliott

Brown

CA.

Hypertension and the kidney. In: Elliott

Syme

Jepson

(eds). Hypertension in the dog and cat. Springer, 2020, pp 171–186.

39.

Chetboul

Lefebvre

Pinhas

et al. Spontaneous feline hypertension: clinical and echocardiographic abnormalities, and survival rate. J Vet Intern Med 2003; 17: 89–95.

40.

Henik

Stepien

Bortnowski

HB.

Spectrum of M-mode echocardiographic abnormalities in 75 cats with systemic hypertension. J Am Anim Hosp Assoc 2004; 40: 359–363.

41.

Littman

MP.

Spontaneous systemic hypertension in 24 cats. J Vet Intern Med 1994; 8: 79–86.

42.

Snyder

Sadek

Jones

GL.

Effect of amlodipine on echocardiographic variables in cats with systemic hypertension. J Vet Intern Med 2001; 15: 52–56.

43.

Elliott

Barber

Syme

et al. Feline hypertension: clinical findings and response to antihypertensive treatment in 30 cases. J Small Anim Pract 2001; 42: 122–129.

44.

Flora

Tang

Smith

et al. Cardiac pathology associated with hypertension and chronic kidney disease in aged cats. J Comp Pathol 2025; 216: 40–49.

45.

Hoehne

Hopper

Epstein

. Retrospective evaluation of the severity of and prognosis associated with potassium abnormalities in dogs and cats presenting to an emergency room (January 2014–August 2015): 2441 cases. J Vet Emerg Crit Care (San Antonio) 2019; 29: 653–661.

46.

Coady

Fletcher

Goggs

Severity of ionized hypercalcemia and hypocalcemia is associated with etiology in dogs and cats. Front Vet Sci 2019; 6: 276. DOI: 10.3389/fvets.2019.00276.

47.

Savary

Price

Vaden

. Hypercalcemia in cats: a retrospective study of 71 cases (1991–1997). J Vet Intern Med 2000; 14: 184–189.

48.

Lee

Chan

Hsu

et al. Prognostic factors and a prognostic index for cats with acute kidney injury. J Vet Intern Med 2012; 26: 500–505.

49.

DiBartola

Rutgers

Zack

et al. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973– 1984). J Am Vet Med Assoc 1987; 190: 1196–1202.

50.

Elliott

Barber

PJ.

Feline chronic renal failure: clinical findings in 80 cases diagnosed between 1992 and 1995. J Small Anim Pract 1998; 39: 78–85.

51.

Barber

Elliott

Feline chronic renal failure: calcium homeostasis in 80 cases diagnosed between 1992 and 1995. J Small Anim Pract 1998; 39: 108–116.

52.

Weiss

Shivkumar

Electrophysiology of hypokalemia and hyperkalemia. Circ Arrhythm Electrophysiol 2017; 10. DOI: 10.1161/CIRCEP.116.004667.

53.

Tag

Day

TK.

Electrocardiographic assessment of hyperkalemia in dogs and cats. J Vet Emerg Crit Care 2008; 18: 61–67.

54.

DiBartola

SP.

Management of hypokalaemia and hyperkalaemia. J Feline Med Surg 2001; 3: 181–183.

55.

Fabiato

Calcium and cardiac excitation–contraction coupling. Ann Rev Physiol 1979; 41: 473–484.

56.

Szedlak

Steele

Hopkins

PM.

Cardiac muscle physiology. BJA Educ 2023; 23: 350–357.

57.

Ghent

Judson

Rosansky

SJ.

Refractory hypotension associated with hypocalcemia and renal disease. Am J Kidney Dis 1994; 23: 430–432.

58.

Lang

Fellner

Neumann

et al. Left ventricular contractility varies directly with blood ionized calcium. Ann Intern Med 1988; 108: 524–529.

59.

Fang

Ginsberg

Sugatani

et al. Early chronic kidney disease-mineral bone disorder stimulates vascular calcification. Kidney Int 2014; 85: 142–150.

60.

Kovesdy

Kuchmak

et al. Outcomes associated with serum calcium level in men with non-dialysis-dependent chronic kidney disease. Clin J Am Soc Nephrol 2010; 5: 468–476.

61.

Shanahan

Crouthamel

Kapustin

et al. Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 2011; 109: 697–711.

62.

Tentori

Blayney

Albert

et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008; 52: 519–530.

63.

Foster

JD.

Update on mineral and bone disorders in chronic kidney disease. Vet Clin North Am Small Anim Pract 2016; 46: 1131–1149.

64.

Tang

Geddes

Jepson

et al. A feline-focused review of chronic kidney diseasemineral and bone disorders – part 2: pathophysiology of calcium disorder and extraosseous calcification. Vet J 2021; 275. DOI: 10.1016/j.tvjl.2021.105718.

65.

Salera

Merkel

Bellasi

et al. Pathophysiology of chronic kidney diseasemineral bone disorder (CKD-MBD): from adaptive to maladaptive mineral homeostasis. Clin Kidney J 2025; 18 Suppl 1: i3–i14.

66.

King

Tasker

Gunn-Moore

et al. Prognostic factors in cats with chronic kidney disease. J Vet Intern Med 2007; 21: 906–916.

67.

Geddes

Elliott

Syme

HM.

Relationship between plasma fibroblast growth factor-23 concentration and survival time in cats with chronic kidney disease. J Vet Intern Med 2015; 29: 1494–1501.

68.

Chakrabarti

Syme

Elliott

Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med 2012; 26: 275–281.

69.

Hruska

Mathew

Lund

et al. Hyperphosphatemia of chronic kidney disease. Kidney Int 2008; 74: 148–157.

70.

Seiler

Reichart

Roth

et al. FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol Dial Transplant 2010; 25: 3983–3989.

71.

Kendrick

Cheung

Kaufman

et al. FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 2011; 22: 1913–1922.

72.

Elliott

Therapeutics of managing reduced red cell mass associated with chronic kidney disease – is there a case for earlier intervention?

J Vet Pharmacol Ther 2023; 46: 145–157.

73.

Anand

IS.

Anemia and chronic heart failure implications and treatment options. J Am Coll Cardiol 2008; 52: 501–511.

74.

Wilson

Jasani

Wagner

et al. Signs of left heart volume overload in severely anaemic cats. J Feline Med Surg 2010; 12: 904–909.

75.

International Renal Interest Society. IRIS guidelines. www.iris-kidney.com/iris-guidelines-1 (2023, accessed 3 June 2025).

76.

Chalhoub

Langston

Farrelly

The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases. J Vet Intern Med 2012; 26: 363–369.

77.

Cowgill

James

Levy

et al. Use of recombinant human erythropoietin for management of anemia in dogs and cats with renal failure. J Am Vet Med Assoc 1998; 212: 521–528.

78.

Charles

Sussenberger

Settje

et al. Use of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, in chronic kidney disease-associated anemia in cats. J Vet Intern Med 2024; 38: 197–204.

79.

Zhang

Wang

JG.

Hypertension induced by hypoxia-inducible factor prolyl hydroxylase inhibitors in treating anemia in patients with chronic kidney disease: a minireview. J Clin Hypertens (Greenwich) 2024; 26: 1375–1383.

80.

Brewster

Setaro

Perazella

MA.

The renin–angiotensin–aldosterone system: cardiorenal effects and implications for renal and cardiovascular disease states. Am J Med Sci 2003; 326: 15–24.

81.

Levens

Peach

Carey

RM.

Role of the intrarenal renin–angiotensin system in the control of renal function. Circ Res 1981; 48: 157–167.

82.

Carey

RM.

The intrarenal renin–angiotensin system in hypertension. Adv Chronic Kidney Dis 2015; 22: 204–210.

83.

Mitani

Yabuki

Sawa

et al. Intrarenal distributions and changes of angiotensin-converting enzyme and angiotensin-converting enzyme 2 in feline and canine chronic kidney disease. J Vet Med Sci 2014; 76: 45–50.

84.

Mitani

Yabuki

Taniguchi

et al. Association between the intrarenal reninangiotensin system and renal injury in chronic kidney disease of dogs and cats. J Vet Med Sci 2013; 75: 127–133.

85.

Lourenco

Coleman

Berghaus

et al. Characterization of the intrarenal renin– angiotensin system in cats with naturally occurring chronic kidney disease. J Vet Intern Med 2022; 36: 647–655.

86.

Kirch

Kohler

Mutschler

et al. Pharmacokinetics of atenolol in relation to renal function. Eur J Clin Pharmacol 1981; 19: 65–71.

87.

Salmon

Coleman

Lynn

et al. Single-and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats. J Vet Cardiol 2024; 51: 86–96.

88.

Sleeper

O’Donnell

Fitzgerald

et al. Pharmacokinetics of furosemide after intravenous, oral and transdermal administration to cats. J Feline Med Surg 2019; 21: 882–886.

89.

Roche-Catholy

Paepe

Devreese

et al. Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats. J Vet Intern Med 2022; 36: 1782–1791.

90.

Gehr

Rudy

Matzke

et al. The pharmacokinetics of intravenous and oral torsemide in patients with chronic renal insufficiency. Clin Pharmacol Ther 1994; 56: 31–38.

91.

Lefebvre

Laroute

Concordet

et al. Effects of renal impairment on the disposition of orally administered enalapril, benazepril, and their active metabolites. J Vet Intern Med 1999; 13: 21–27.

92.

King

Strehlau

Wernsing

et al. Effect of renal insufficiency on the pharmacokinetics and pharmacodynamics of benazepril in cats. J Vet Pharmacol Ther 2002; 25: 371–378.

93.

Boehringer Ingelheim Vetmedica

. Vetmedin (pimobendan) chewable tablets [package insert]. St Joseph, MO: Boehringer Ingelheim Vetmedica, 2012.

94.

Murphy

Williams

Kau

DL.

Disposition of dobutamine in the dog. J Pharmacol Exp Ther 1976; 199: 423–431.

95.

Lins

Broekhuysen

Necciari

et al. Pharmacokinetic profile of C-labeled clopido-grel. Semin Thromb Hemost 1999; 25: 29–33.

96.

Kreutz

Pharmacodynamic and pharmacokinetic basics of rivaroxaban. Fundam Clin Pharmacol 2012; 26: 27–32.

97.

Wienen

Entzeroth

van Meel

JCA

et al. A review on telmisartan: a novel, long-acting angiotensin II-receptor antagonist. Cardiovasc Drug Rev 2000; 18: 127–156.

98.

Ebner

Schanzle

Weber

et al. In vitro glucuronidation of the angiotensin II receptor antagonist telmisartan in the cat: a comparison with other species. J Vet Pharmacol Ther 2013; 36: 154–160.

99.

Stopher

Beresford

Macrae

et al. The metabolism and pharmacokinetics of amlodipine in humans and animals. J Cardio vasc Pharmacol 1988; 12 Suppl 7: 55–59.

100.

Ortiz

Navarro-Gonzalez

Nunez

et al. The unmet need of evidence-based therapy for patients with advanced chronic kidney disease and heart failure: position paper from the Cardiorenal Working Groups of the Spanish Society of Nephrology and the Spanish Society of Cardiology. Clin Kidney J 2022; 15: 865–872.

101.

Shlipak

Browner

Noguchi

et al. Comparison of the effects of angiotensin converting-enzyme inhibitors and beta blockers on survival in elderly patients with reduced left ventricular function after myocardial infarction. Am J Med 2001; 110: 425–433.

102.

McAlister

Ezekowitz

Tonelli

et al. Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study. Circulation 2004; 109: 1004–1009.

103.

Klainbart

Agi

Bdolah-Abram

et al. Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis. J Am Vet Med Assoc 2017; 251: 1025–1034.

104.

Muller

Penninck

Webster

et al. Abdominal ultrasonographic findings of cats with feline infectious peritonitis: an update. J Feline Med Surg 2023; 25. DOI: 10.1177/1098612X231216000.

105.

Carter

Pariaut

Snook

et al. Multicentric lymphoma mimicking decompensated hypertrophic cardiomyopathy in a cat. J Vet Intern Med 2008; 22: 1345–1347.

106.

Sangster

Panciera

Abbott

et al. Cardiac biomarkers in hyperthyroid cats. J Vet Intern Med 2014; 28: 465–472.

107.

Geddes

Aguiar

Feline comorbidities: balancing hyperthyroidism and concurrent chronic kidney disease. J Feline Med Surg 2022; 24: 641–650.

108.

Scudder

Church

Feline comorbidities: hypersomatotropism-induced diabetes in cats. J Feline Med Surg 2024; 26. DOI: 10.1177/1098612X241226690.

109.

Javadi

Djajadiningrat-Laanen

Kooistra

et al. Primary hyperaldosteronism, a mediator of progressive renal disease in cats. Domest Anim Endocrinol 2005; 28: 85–104.

110.

Ash

Harvey

Tasker

Primary hyperaldosteronism in the cat: a series of 13 cases. J Feline Med Surg 2005; 7: 173–182.

111.

Chen

Avital

Peterson

et al. Urinary Cystatin B as a marker of acute kidney injury in cats. Vet J 2024; 308: DOI: 10.1016/j.tvjl.2024.106262.

112.

Hall

Forman

Bobe

et al. The impact of periodontal disease and dental cleaning procedures on serum and urine kidney biomarkers in dogs and cats. PloS One 2021; 16. DOI: 10.1371/journal.pone.0255310.

113.

KuKanich

George

Roush

et al. Effects of low-dose meloxicam in cats with chronic kidney disease. J Feline Med Surg 2021; 23: 138–148.

114.

Wang

Hsu

et al. Neutrophil gelatinase-associated lipocalin in cats with naturally occurring chronic kidney disease. J Vet Intern Med 2017; 31: 102–108.

115.

Debruyn

Haers

Combes

et al. Ultrasonography of the feline kidney: technique, anatomy and changes associated with disease. J Feline Med Surg 2012; 14: 794–803.

116.

Griffin

Feline abdominal ultrasonography: what’s normal? what’s abnormal? The kidneys and perinephric space. J Feline Med Surg 2020; 22: 409–427.

117.

Schober

Maerz

Ludewig

et al. Diagnostic accuracy of electrocardiography and thoracic radiography in the assessment of left atrial size in cats: comparison with transthoracic 2-dimensional echocardiography. J Vet Intern Med 2007; 21: 709–718.

118.

Guglielmini

Diana

Thoracic radiography in the cat: identification of cardiomegaly and congestive heart failure. J Vet Cardiol 2015; 17 Suppl 1: 87–101.

119.

Payne

Borgeat

Connolly

et al. Prognostic indicators in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2013; 27: 1427–1436.

120.

Porciello

Rishniw

Herndon

et al. Cardiac troponin I is elevated in dogs and cats with azotaemia renal failure and in dogs with non-cardiac systemic disease. Aust Vet J 2008; 86: 390–394.

121.

Lalor

Connolly

Elliott

et al. Plasma concentrations of natriuretic peptides in normal cats and normotensive and hypertensive cats with chronic kidney disease. J Vet Cardiol 2009; 11 Suppl 1: 71–79.

122.

Rishniw

Should we be screening cats for cardiomyopathy? If so, how?

J Am Vet Med Assoc 2022; 260: 1626–1630.

123.

Rush

Freeman

Fenollosa

et al. Population and survival characteristics of cats with hypertrophic cardiomyopathy: 260 cases (1990–1999). J Am Vet Med Assoc 2002; 220: 202–207.

124.

Cote

Edwards

Ettinger

et al. Management of incidentally detected heart murmurs in dogs and cats. J Vet Cardiol 2015; 17: 245–261.

125.

Kumric

Kurir

Bozic

et al. Pathophysiology of congestion in heart failure: a contemporary review. Card Fail Rev 2024; 10. DOI: 10.15420/cfr.2024.07.

126.

Patel

Sharma

Prasad

et al. Heart failure with preserved ejection fraction with CKD: a narrative review of a multispecialty disorder. Kidney Med 2023; 5. DOI: 10.1016/j.xkme.2023.100705.

127.

DeBiasi

Feller-Kopman

Physiologic basis of symptoms in pleural disease. Semin Respir Crit Care Med 2019; 40: 305–313.

128.

Spalla

Payne

Borgeat

et al. Mitral annular plane systolic excursion and tricuspid annular plane systolic excursion in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2017; 31: 691–699.

129.

Ward

Kussin

Tropf

et al. Retrospective evaluation of the safety and tolerability of pimobendan in cats with obstructive vs nonobstructive cardiomyopathy. J Vet Intern Med 2020; 34: 2211–2222.

130.

Santiago

Freeman

Rush

JE.

Cardiac cachexia in cats with congestive heart failure: prevalence and clinical, laboratory, and survival findings. J Vet Intern Med 2020; 34: 35–44.

131.

Saker

KE.

Nutritional concerns for cancer, cachexia, frailty, and sarcopenia in canine and feline pets. Vet Clin North Am Small Anim Pract 2021; 51: 729–744.

132.

Elliott

Rawlings

Markwell

et al. Survival of cats with naturally occur ring chronic renal failure: effect of dietary management. J Small Anim Pract 2000; 41: 235–242.

133.

Obi

Tortorici

et al. Dietary protein intake and chronic kidney disease. Curr Opin Clin Nutr Metab Care 2017; 20: 77–85.

134.

Ross

Osborne

Kirk

et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc 2006; 229: 949–957.

135.

Churchill

Eirmann

Senior pet nutrition and management. Vet Clin North Am Small Anim Pract 2021; 51: 635–651.

136.

Segev

Cortellini

Foster

et al. International Renal Interest Society best practice consensus guidelines for the diagnosis and management of acute kidney injury in cats and dogs. Vet J 2024; 305. DOI: 10.1016/j.tvjl.2024.106068.

137.

Ljungvall

Rishniw

Porciello

et al. Sleeping and resting respiratory rates in healthy adult cats and cats with subclinical heart disease. J Feline Med Surg 2014; 16: 281–290.

138.

Porciello

Rishniw

Ljungvall

et al. Sleeping and resting respiratory rates in dogs and cats with medically-controlled left-sided congestive heart failure. Vet J 2016; 207: 164–168.