Cardiorenal syndrome

Definition. Cardiorenal syndrome (CRS) is a group of disorders of the heart and kidneys in which acute or chronic dysfunction of one organ induces acute or chronic dysfunction of the other. It is bidirectional, and its recognition matters because the presence of renal dysfunction is one of the strongest independent predictors of mortality in heart failure, and because it constrains the very treatments (diuretics, ACE inhibitors, MRAs) that heart failure requires.

Classification (Ronco).

Pathophysiology. The traditional model of a "low forward flow" reducing renal perfusion is now known to be secondary. The dominant mechanism is renal VENOUS CONGESTION — a raised central venous pressure is transmitted back to the renal veins, raising renal interstitial and intracapsular pressure, reducing the transrenal perfusion gradient and hence the glomerular filtration rate. Elevated intra-abdominal pressure from ascites and visceral oedema compounds this. Additional mechanisms: neurohormonal activation (renin– angiotensin–aldosterone and sympathetic overactivity) causing sodium and water retention and efferent arteriolar constriction; systemic inflammation and oxidative stress; endothelial dysfunction with reduced nitric oxide; anaemia and iron deficiency, forming the "cardiorenal anaemia syndrome"; and drug-induced injury from NSAIDs, contrast media and over-diuresis. In the older patient reduced renal reserve, nephrosclerosis, and reduced GFR that is masked by low muscle mass make all of this more likely.

Clinical features and assessment. Features of congestion — raised JVP, peripheral and sacral oedema, hepatomegaly and ascites, weight gain, orthopnoea — coexisting with features of renal dysfunction — rising creatinine and urea, oliguria, hyperkalaemia, metabolic acidosis, anaemia. The critical bedside distinction is between the CONGESTED patient (raised JVP, dilated IVC, oedema — needs MORE decongestion) and the HYPOVOLAEMIC over-diuresed patient (flat JVP, postural drop, dry mucosae — needs LESS diuretic), because the creatinine rises in both. Assess with daily weight, strict fluid balance, JVP, postural blood pressure, IVC diameter and lung ultrasound B-lines. Investigations: urea, electrolytes, creatinine and eGFR, urinalysis with urine protein-creatinine ratio, urine sodium, full blood count and iron studies, natriuretic peptides, renal ultrasound, echocardiography, and review for nephrotoxins. Note that a rise in creatinine during effective decongestion ("pseudo-worsening renal function") is common, is haemodynamic rather than structural, and is NOT associated with worse outcome provided congestion is being relieved.

Management — decongestion. Intravenous loop diuretics are the cornerstone. Give as a bolus or continuous infusion at 1–2.5 times the usual home oral dose; oral bioavailability is unreliable in gut oedema. For diuretic resistance, use sequential nephron blockade — add a thiazide-type diuretic (metolazone or hydrochlorothiazide) 30 minutes before the loop diuretic, add an MRA, and consider acetazolamide. Restrict sodium and fluid. Ultrafiltration is reserved for genuinely diuretic-resistant congestion; it removes isotonic fluid but has not shown superiority over stepped pharmacological care (CARRESS-HF). Renal replacement therapy for refractory hyperkalaemia, acidosis, uraemia or fluid overload. Monitor daily weight, fluid balance, renal function and electrolytes.

Management — disease-modifying therapy and the drugs to keep or stop. Do NOT reflexively stop ACE inhibitors, ARBs or MRAs for a modest creatinine rise — a rise of up to about 30% with stable potassium is acceptable and these drugs confer long-term cardiac and renal benefit; halve the dose and monitor rather than stopping outright. Do stop them for a rise beyond 30%, refractory hyperkalaemia or symptomatic hypotension. Stop NSAIDs and other nephrotoxins, and minimise contrast exposure. Continue or start an SGLT2 inhibitor, which reduces both heart failure and renal endpoints and may cause a small early reversible "dip" in eGFR that should not prompt discontinuation. Treat anaemia and iron deficiency with intravenous iron. Manage hyperkalaemia with dietary advice and a potassium binder (patiromer or sodium zirconium cyclosilicate) so that RAAS inhibition can be maintained. Treat the precipitant — infection, arrhythmia, ischaemia, obstruction. Involve nephrology and cardiology jointly, and in the frail older patient with advanced dual organ failure, undertake advance care planning and consider a conservative, symptom-focused pathway rather than dialysis.

Combination diuretic therapy up front, and non-steroidal MRAs, have changed cardiorenal management. The ADVOR trial showed that adding intravenous acetazolamide 500 mg daily to loop diuretics significantly increased successful decongestion and shortened hospital stay in acute decompensated heart failure with volume overload, and CLOROTIC showed that adding hydrochlorothiazide improved weight loss and diuretic response — both are now reflected in the 2023 ESC heart failure focused update, which endorses early combination diuretic therapy for congestion rather than escalating a loop diuretic alone. In parallel, FIDELIO-DKD and FIGARO-DKD established that finerenone reduces both renal progression and cardiovascular events in chronic kidney disease with type 2 diabetes with less hyperkalaemia than spironolactone, and FINEARTS-HF (NEJM 2024) extended this benefit to HFmrEF and HFpEF — giving, for the first time, a single agent that protects both organs in the cardiorenal patient.