Scientific and historical introduction to continuous kidney replacement therapy
Origins and historical development
Continuous kidney replacement therapy initially developed from research into ultrafiltration and convective transport. In 1967, Henderson and colleagues published a description of blood purification by ultrafiltration with fluid replacement, an early contribution to the development of haemofiltration techniques. [1]
In 1974, Silverstein and colleagues published a study entitled ‘Treatment of severe fluid overload by ultrafiltration’ [2]. Kramer and colleagues’ paper, published in 1977, is an early clinical description of continuous arteriovenous haemofiltration (CAVH); the work was conducted in Göttingen, in what was then West Germany. A capillary haemofilter was used, and the arteriovenous pressure gradient drove blood through the circuit without a blood pump.
The report focused on fluid removal in patients with diuretic-resistant fluid overload. It described a blood flow of approximately 100 mL/min, an ultrafiltration rate of 200–600 mL/h, and the possibility of continuing to use the filter for up to 48 hours. [3]
In 1980, Kramer and colleagues described their experience in anuric intensive-care patients. They concluded that CAVH enabled control of fluid balance in patients who had not responded to diuretics, and also reported its use to manage uraemia and hypernatraemia. [4]
CAVH relied on the patient’s arterial pressure through an arterial access. Historical reviews report that limited toxin removal in highly catabolic states and problems with arterial access prompted the development of venovenous techniques driven by a blood pump.
Pump-driven CVVH techniques emerged in the mid-1980s and subsequently became more widespread as double-lumen venous catheters and pumping systems became available. [5,6,10]
Diffusion was added to convection through the development of continuous arteriovenous haemodialysis (CAVHD); Geronemus and Schneider’s description of this technique was published in 1984.
As circuits transitioned to venovenous access, the modalities now known as CVVH, CVVHD and CVVHDF took shape. Each name denotes the predominant or employed transport mechanism: convection in CVVH, diffusion in CVVHD, and their combination in CVVHDF. [5,7]
What continuous kidney replacement therapy means
This article uses the term continuous dialysis or continuous kidney replacement therapy (CKRT).
Continuous Kidney Replacement Therapy. The terms continuous dialysis, continuous kidney replacement therapy, and continuous renal replacement therapy (CRRT) are also widely used in the literature. The word ‘continuous’ should not be understood to mean that treatment is never interrupted: the term describes a prolonged treatment modality compared with intermittent dialysis sessions, and the actual delivered treatment duration may be affected by clinical or technical interruptions. [5,8]
In its nomenclature recommendations, KDIGO advises using ‘kidney’ rather than ‘renal’ when describing kidney function and disease, and identifies ‘kidney replacement therapy (KRT)’ as the preferred term instead of ‘renal replacement therapy (RRT)’.
CKRT is therefore used here, while acknowledging that CRRT remains common in publications and earlier guidelines. [8]
Selecting the modality and what the evidence demonstrates
The 2012 KDIGO guidelines recommend using continuous and intermittent treatments as complementary options in acute kidney injury. They suggest CKRT rather than standard intermittent treatment in haemodynamically unstable patients, and in patients with acute brain injury, raised intracranial pressure or generalised cerebral oedema; both recommendations are graded 2B. The guidelines explain that gradual fluid and solute removal provides the physiological rationale for preferring a continuous modality in these situations. [7]
However, a recommendation about modality selection does not mean that trials have demonstrated superior clinical outcomes with CKRT. An analysis of randomised trials involving 30 trials and 3774 patients found no clear difference in mortality between CKRT and intermittent haemodialysis, and no clear difference in hypotension during treatment was established. The certainty of evidence for most comparisons was classified as low to moderate. The analysis suggested that kidney recovery might be greater with CKRT than with intermittent dialysis, but the estimate was inconclusive. A consistent survival or kidney-recovery benefit therefore cannot be asserted. [9]
Accordingly, modality selection remains dependent on the clinical condition, the treatment goal, the ability to tolerate the rate of fluid removal and changes in solute concentration, and the unit’s experience and resources. KDIGO acknowledges that no single modality is suitable for every patient with acute kidney injury. [7]
Clinical uses and practical limitations
In acute brain injury, raised intracranial pressure or generalised cerebral oedema, KDIGO suggests CKRT rather than intermittent treatment. The guidelines note that rapid changes in blood pressure or solute concentration during intermittent treatment may affect cerebral perfusion pressure or increase oedema and intracranial pressure. This rationale was based on observational data and clinical reports as well as physiological considerations. [7]
This is supported by the fact that urea is distributed throughout total body water but crosses the blood–brain barrier only slowly. Excessively rapid removal of urea from the circulation using intermittent haemodialysis (IHD) may therefore promote movement of plasma water into the brain. The so-called reverse urea effect can cause or exacerbate raised intracranial pressure, with potentially serious neurological consequences.
Severe liver failure is also associated with cerebral oedema and raised intracranial pressure; CKRT should therefore similarly be preferred in these patients. However, the cited KDIGO recommendation does not list liver failure alone as an independent indication for preferring CKRT. In patients with acute kidney injury and liver failure or lactic acidosis, the guidelines recommend bicarbonate rather than lactate in dialysis or replacement fluid. This recommendation concerns fluid composition and does not by itself demonstrate that CKRT is superior to other modalities. [7]
A continuous modality may allow ongoing control of fluid balance in an oliguric or anuric patient receiving therapeutic or nutritional fluids (Total Parenteral Nutrition, TPN). Fluid control, together with management of uraemia and certain electrolyte disturbances, was among the uses documented in Kramer’s report in intensive-care patients. This does not, however, make CKRT the only option: the decision remains individualised according to the clinical condition and available resources. [4,7]
Because fluid and solute removal during CKRT is gradual, it may not achieve the correction rate required when there is a clinical need for rapid removal of a dialysable substance or correction of a life-threatening disturbance. KDIGO describes rapid removal of toxins and low-molecular-weight substances as a potential advantage of intermittent treatment. The modality should therefore be selected according to the problem being treated, rather than assuming absolute superiority of one modality. [7]