Renal replacement therapy II

The treatment of renal failure includes dietary modification, drug treatment and hormonal supplements as well as renal transplantation. The rationale for these therapies and the associated problems likely to present to the GP are given practical consideration.     

Renal replacement therapy. I

Virtually all patients with end-stage renal disease can achieve a better quality of life with renal replacement therapy. Given that a group practice with 10,000 patients may have two dialysis or transplant patients, it is important to know what is on offer. The first stage of renal replacement therapy is dialysis and the principles and problems are discussed here. In the next issue dietary management, drug therapy and the role of transplantation will be considered.     

Renal replacement therapy I: indications and timing

The indications for initiation of renal replacement therapy in acute renal failure are controversial. Although volume overload, metabolic acidosis, hyperkalemia and other electrolyte disturbances, and overt uremic manifestations are commonly accepted indications for renal replacement therapy, specific criteria for initiation of therapy based on these conditions are highly subjective. Progressive azotemia in the absence of overt uremia is another common indication for renal replacement therapy although there is no consensus on the degree of azotemia that warrants initiation of therapy. The clinical data regarding timing and initiation of renal support in patients who have acute renal failure are reviewed. Definitive resolution of the appropriate indications and timing for initiation of renal replacement therapy in acute renal failure requires prospective evaluation in a randomized clinical trial.     

Renal failure and renal replacement therapy

Continuous renal replacement therapy is an effective means for fluid and solute management in ARF/MOSF. Prospective studies have examined issues of anticoagulation, the impact of replacement/dialysis, the effects of bicarbonate-versus lactate-based solutions, and nutritional and medication clearance. Speculation and bias exists concerning when and for what indications CRRT should be initiated. Many clinicians, supported by data from Ronco and Goldstein, would contest that early institution is better if the risks (eg, access, anticoagulation) are minimal and the possible benefits are maximal. The authors, examining the issues as an intensivist and as a nephrologist, believe that early institution, aggressive replacement/dialysis, and use of citrate-based replacement fluids provide substantive advantages. With the advent of Ronco's recent data on sepsis managed with filtration and plasma absorption, the indication for use of CRRT in MOSF may become more evident regardless of the presence or absence of ARF.     

Cefepime and continuous renal replacement therapy (CRRT): in vitro permeability of two CRRT membranes and pharmacokinetics in four critically ill patients

BACKGROUND: Cefepime is a fourth-generation cephalosporin with a broad spectrum of antimicrobial activity against gram-positive and gram-negative micro-organisms. It is a useful option for treating infections in critically ill patients in intensive care due to its high degree of activity and its tolerability. OBJECTIVE: The aim of this study was to characterize in vitro the permeability to cefepime of 2 membranes frequently used in continuous renal replacement therapies (CRRTs). An in vivo study was also carried out to determine the pharmacokinetics of cefepime in critically ill patients undergoing CRRT. METHODS: In vitro procedures were conducted in 3 different fluids using polyacrylonitrile (AN69) or polysulfone (PS) membranes. Continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) were simulated. Four male patients undergoing CVVH or continuous venovenous hemodiafiltration, who received 2000 mg of cefepime intravenously every 8 hours, entered the in vivo study. Prefilter and ultrafiltrate samples were collected, and concentrations of cefepime were measured using high-performance liquid chromatography. The sieving coefficient (Sc), defined as the fraction of drug eliminated across the membrane, and the saturation coefficient (Sa), defined as the fraction of drug diffused through the membrane to the dialysate fluid, were analyzed. Pharmacokinetic parameters were determined according to a noncompartmental analysis. RESULTS: The patients ranged in age from 18 to 75 years and weighed from 65 to 80 kg. By analyzing Sc and Sa values in the in vitro procedures, no differences were detected in the permeability of AN69 or PS membranes to cefepime in CVVH or CVVHD. Sc/Sa values were between 0.93 and 1.03 in Ringer's lactate and in bovine albumin-containing Ringer's lactate samples, but Sc/Sa values were lower in plasma samples (0.82-0.95). In the in vivo portion of the study, the patients' mean (SD) Sc/Sa value was 0.76 (0.21) and correlated well with the fraction unbound to proteins (0.79 [0.09]). Clearance by CRRT (mean [SD]) was 29.0 (16.8)% of the total clearance. Serum elimination t(1/2) was 4.6 (0.9) hours, and the volume of distribution at steady state was 0.6 (0.3) L/kg (mean [SD] values). CONCLUSIONS: Cefepime was significantly removed by CRRT. No significant differences were found in the Sc or Sa of cefepime between AN69 and PS membranes used in the CVVH or CVVHD procedures. The clearance of cefepime by CRRT must be considered when dosing critically ill patients.     

Renal replacement therapy in the critical care unit

Acute renal failure is common in critically ill patients. Many intensive care unit patients require renal replacement therapy (RRT). Hemodialysis can be performed as intermittent treatments or as continuous RRT, which can be customized to clinical goals by the use of carefully designed replacement fluids and hemodialysates. The available forms of RRT are reviewed, with emphasis on the clinical indications that contribute to the choice and design of therapy. Practical issues and troubleshooting are discussed, as are available options for anticoagulation during RRT. Consideration is given to modality choice, hemodynamic issues, costs, and physiologic outcomes.     

Renal replacement therapy for acute renal failure.

Mortality from acute renal failure (ARF) remains very high and is associated with the development of multisystem failure. Technical developments in haemodialysis machines and dialyser membranes have reduced complications associated with haemodialysis. However, some patients are too unstable to be haemodialysed successfully. Continuous haemofiltration and continuous arterio-venous (or veno-venous) haemodialysis can be performed on Intensive Care Units in hospitals without the availability of a Renal Unit. These techniques provide more effective and controlled removal of fluid and uraemic toxins. There are now few indications for the use of peritoneal dialysis. These new developments have facilitated easier management of the unstable patient with acute renal failure. Whether the prognosis of acute renal failure patients will be improved remains to be determined.     

Renal replacement therapy in acute infectious renal insufficiency

A modern view on renal failure in patients with infectious diseases is presented and possibilities of various methods of renal replacement therapy are evaluated. The authors emphasize the obligatory combination of etiotropic and pathogenetic therapy. A clinical case is presented: a patient with tropical and 3-day malaria was effectively treated by high-flow intermittent hemofiltration.     

Renal replacement therapy in acute kidney injury: controversy and consensus

Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future.     

Quality indicators of continuous renal replacement therapy (CRRT) care in critically ill patients: a systematic review

Objectives

Renal replacement therapy is increasingly utilized in the intensive care unit (ICU), of which continuous renal replacement therapy (CRRT) is most common. Despite CRRT being a relatively invasive and resource intensive technology, there remains wide practice variation in its application. This systematic review appraised the evidence for quality indicators (QIs) of CRRT care in critically ill patients.

Design

A comprehensive search strategy was developed and performed in five citation databases (Medline, Embase, CINAHL, Cochrane Library, and PubMed) and select grey literature sources. Two reviewers independently screened, selected, and extracted data using standardized forms. Each retrieved citation was appraised for quality using the Newcastle–Ottawa Scale (NOS) and Cochrane risk of bias tool. Data were summarized narratively.

Measurements and main results

Our search yielded 8374 citations, of which 133 fulfilled eligibility. This included 97 cohort studies, 24 randomized controlled trials, 10 case-control studies, and 2 retrospective medical audits. The quality of retrieved studies was generally good. In total, 18 QIs were identified that were mentioned in 238 instances. Identified QIs were classified as related to structure (n = 4, 22.2 %), care processes (n = 9, 50.0 %), and outcomes (n = 5, 27.8 %). The most commonly mentioned QIs focused on filter lifespan (n = 98), small solute clearance (n = 46), bleeding (n = 30), delivered dose (n = 19), and treatment interruption (n = 5). Across studies, the definitions used for QIs evaluating similar constructs varied considerably. When identified, QIs were most commonly described as important (n = 144, 48.3 %), scientifically acceptable (n = 32, 10.7 %), and useable and/or feasible (n = 17, 5.7 %) by their primary study authors.

Conclusions

We identified numerous potential QIs of CRRT care, characterized by heterogeneous definitions, varying quality of derivation, and limited evaluation. Further study is needed to prioritize a concise inventory of QIs to measure, improve, and benchmark CRRT care for critically ill patients.

Systematic review registration

PROSPERO CRD42015015530.

     

Renal replacement therapy: to treat,or not to treat,that is the question...

When to commence renal replacement therapy (RRT) in the critically ill remains an unresolved issue. The study by Thakar and colleagues sheds some light on current practice through an international survey, demonstrating physicians'' inclination to start RRT earlier when the severity of disease is higher. However, Clec''h and co-workers investigated the effect of RRT on hospital survival by performing a propensity analysis on the large multicentre French OUTCOMEREA database. They demonstrate that RRT does not confer survival benefit, with a delay in initiation being proposed as a contributing factor.Timing of initiation of renal replacement therapy (RRT) is currently one of the major unresolved topics in critical care nephrology and this is addressed through different approaches in a previous issue of Critical Care [1,2]. Thakar and colleagues [1] performed an international survey predominantly among North American nephrologists consulting in intensive care. They questioned practice patterns for the initiation of RRT using three case scenarios representing patients with increased severity of disease and, by implication, a higher probability of mortality. The majority of the 172 respondents (70% USA) expressed a reticence in commencing RRT early given the lack of evidence, preferring to base their decision on absolute levels of creatinine or blood urea nitrogen (BUN) (>442 μmol/l (>5 mg/dl), >35.6 mmol/l (>100 mg/dl), respectively) rather than any relative rise. Despite this, 94% of physicians reported that they would be likely to start dialysis early in patients with the highest disease burden with early RRT described as a lower BUN on commencing treatment. Thus, the proportion of physicians starting dialysis at a BUN <75 mg/dl tripled in the more severe case. Finally, given a selection of five parameters (BUN, creatinine, urine output, oxygenation and potassium) for starting RRT, the latter two were given the highest priority with oxygen saturation appearing as the most frequent trigger in severe cases. However, as in most studies of this nature, cohort selection is of great importance. For example, only two nephrologists were also trained in critical care. The responses were substantially influenced by current practice in the US underlined by the significantly higher inclination towards early initiation of RRT in physicians practicing outside the US [1]. These results also differ to a recently published survey among 275, mainly European intensivists [3]. Whereas the median thresholds with regard to serum creatinine (300 μmol/l) or urea (40 mmol/l) were similar, there was a higher priority attached to hyperkalemia, metabolic acidosis and volume overload. Additionally, they demonstrated a trend towards early initiation of RRT, with the majority favouring initiation when a diagnosis of acute kidney injury (AKI) was made based on AKIN (Acute Kidney Injury Network)/RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) criteria, particularly with regard to oliguria [3]. Thus, early treatment was defined by starting RRT within 6 hours after AKI diagnosis according to the AKIN/RIFLE criteria. The perceived importance of oliguria as a trigger for commencing RRT is supported by other studies. For example, the international BEST kidney study group identified oliguria/anuria as the most frequent reason to start RRT [4] and similar results were seen in the RENAL trial where oliguria was the indication to start in 60% of all patients [5].A completely different approach towards initiation of treatment was chosen by Clec''h and co-workers investigating the effect of RRT on hospital survival in the French longitudinal prospective multicenter OUTCOMEREA database [2]. They addressed the question as to whether RRT confers a survival benefit in critically ill patients through sophisticated propensity analyses. Using two different propensity scores the answer was a resounding ''NO''. Do these results mean that RRT should be abandoned? Of course not: RRT definitely does one thing - it clears toxins and re-establishes electrolyte, acid-base and fluid homeostasis. Therefore, the maximum one could expect from provision of RRT would be hospital mortality equal to patients not requiring RRT. However, the occurrence of AKI reflects a higher severity of disease and is independently associated with increased mortality [6-8]. Therefore, observed outcome will always be worse, regardless of how efficiently we replace the failing kidneys. This is clearly supported by the significantly higher modified Severity of Organ Failure score (mSOFA) and Simplified Acute Physiology Score (SAPS) II scores found for patients treated with RRT in both the crude comparison and the two propensity models [2]. Interestingly, one of the main conclusions was to commence RRT earlier based on the finding that delayed RRT, that is, starting 48 hours after reaching maximum RIFLE, was associated with a two-fold increased odds ratio for mortality compared to early or immediate RRT. However, only 12% of all patients treated with RRT fell into the ''late'' category and the median duration from onset of AKI to start of RRT was only one day in this cohort. So, although the data suggest that ''very late RRT'' will be probably detrimental, no reliable conclusions can be drawn regarding the benefit of early or very early initiation of RRT from this study [2]. Lower stages of AKI are associated with a lower mortality; thus, it could be argued that one should not wait until the patient has reached a higher level of AKI before commencing treatment [8,9]. This is compounded by the fact that the maximum AKI stage remains a retrospective diagnosis and cannot be reliably predicted. Nor can patients who will progress to a stage where RRT will be absolutely necessary or those who will recover without the need for RRT [10]. In fact, three smaller randomized controlled trials showed either no benefit with early RRT [11,12] or even an increased mortality compared to standard medical treatment in severe sepsis [13]. In trying to determine which parameter might be the most relevant for starting RRT, Clec''h and colleagues [2] found only oliguria (0.4 L versus 1.3 L) and fluid accumulation (4 L versus 2 L) as significant for patients treated with RRT when performing a matched pair analysis. This again may reflect changes in practice in terms of avoiding a positive fluid balance.The syndrome of AKI continues to gain importance; the numbers of AKI patients requiring RRT have roughly doubled over the past 10 years in the USA [14], which contribute to increased mortality and an increased burden on health care systems. Several surveys and clinical studies reveal significant variations in treatment patterns as well as outcomes, largely dependent on regional or national habits as well as the primary medical speciality delivering RRT in critically ill patients. The practice of using fixed thresholds of creatinine or urea for timing of RRT may be considered a relic from haemodialysis programmes where creatinine is taken as a surrogate for residual function [15]. In critically ill patients with AKI, urea and creatinine are not reliable indicators of renal function given the lack of steady state in terms of production and the influence of catabolism, volume status and production rates, particularly in sepsis [10]. Consequently, physicians treating critically ill patients put an increasing emphasis on volume overload, oliguria, impaired oxygenation and acidosis as triggers for initiation of RRT with a general trend to commence RRT earlier in sicker patients.Despite some progress achieved by recent recommendations [16], no generally accepted consensus as to when to commence RRT exists. Probably the conventional criteria discussed above are not sufficient to discriminate between early and late initiation of RRT and including additional biomarkers indicating renal damage may be required for that. This, however, can only be answered by a future sufficiently powered prospective randomized controlled trial.     

Renal replacement therapy and the kidney: minimizing the impact of renal replacement therapy on recovery of acute renal failure

PURPOSE OF REVIEW: Although renal replacement therapy is the mainstay of supportive care in patients with severe acute renal failure, its performance can have untoward effects that contribute to the prolongation of renal failure or impede the ultimate recovery of renal function. In this review, we categorize the major complications associated with renal replacement therapy and assess their impact on recovery of renal function. RECENT FINDINGS: The major mechanisms by which renal replacement therapy is postulated to delay renal recovery include treatment-associated hemodynamic instability, vascular catheter-related bacteremia and sepsis, and cytokine activation by bioincompatible membranes. Clinical data regarding the role of dialysis catheter infections in delay of renal recovery are lacking. The data regarding the role of membrane biocompatibility and the modality and dose of renal replacement therapy are limited and conflicting. SUMMARY: Clinical recommendations must be limited to the broad admonishment that complications during renal replacement therapy, including hemodynamic instability and catheter-related bacteremia, be minimized by using best clinical practices, while recognizing that the impact of specific practices on recovery of renal function have not been evaluated. The data do not support recommendations regarding utilization of specific membranes or the modality or dose of renal replacement therapy on the basis of their impact on recovery of renal function.     

两种稀释模式肾脏替代治疗MODS患者的效果比较

目的 比较两种稀释模式,前稀释与后稀释方法连续肾脏替代(continuous renalreplacement therapy,CRRT)治疗多器官功能不全(multiple organs dysfunction syndrome,MODS)的效果.方法 32例接受CRRT治疗MODS患者,随机(随机分组法)分组,前稀释方法17例,后稀释方法15例,比较两种模式静脉-静脉血液滤过(CVVH)治疗的净增加肌酐清除率、酸碱平衡紊乱的纠正、对血流动力学参数的影响,以及对两种模式的滤前压、滤器寿命、APACHE Ⅱ评分、病死率等进行比较.结果 前、后稀释模式治疗24h净增加的肌酐清除率分别的(15.6±4.6)mL/min vs.(22.7±4.1)mL/min(P＜0.01);48 h分别为(14.9±3.3)mL/min vs.(8.9±5.3)mL/min(P＜0.05);两种稀释模式治疗24 h后均较治疗前明显纠正患者的酸碱平衡紊乱(P＜0.05),但两组间治疗后差异无统计学意义(P＞0.05);前稀释模式治疗24 h前、后平均动脉压(MAP)为(56.7±9.1)mmHg vs.(69.2±4.6)mmHg(1 mmHg=0.133 kPa)(P＜0.05);前稀释模式治疗24 h前、后多巴胺使用剂量(11.20±3.45)μg·kg-1·min-1 vs.(6.12±3.41)μg·kg-1·min-1(P＜0.05);前、后稀释模式最大滤前压分别为(82.23±9.11)cm H2O vs(110.56±28.14)cm H2O(1 cmH2O=0.098 kPa)(P＜0.05).前、后稀释组滤器寿命分别为(39.00±28.12)h和(25±14.45)h(P＜0.05);前稀释组治疗前后均可改善APACHEⅡ评分(P＜0.05),两组间治疗后APACHEⅡ评分、病死率差异无统计学意义(P＞0.05).结论 前、后稀释模式比较,后者滤过效率高,但最大滤前压高,滤器使用寿命短;而前者能更好地改善血流动力学,减少升压药物用量.两种模式纠正酸碱平衡紊乱效果、对APACHEⅡ评分影响及治疗后的病死率无差异.     

Renal replacement therapy in intensive care units in KwaZulu-Natal Province,South Africa

Background Renal replacement therapy (RRT) is a scarce resource in southern Africa. Critically ill patients are at risk of developing acute kidney injury (AKI), which may require RRT. There are few data on the utilisation of RRT in southern African intensive care units (ICUs). Objectives To determine the indications for initiating RRT in critically ill patients in ICUs in KwaZulu-Natal, South Africa (SA) and to describe the methods and dosing of RRT. Methods A prospective observational study was performed to investigate the indications for initiating, methods and dosing of RRT among patients admitted to four ICUs in KwaZulu-Natal Province, SA. All adult patients were eligible for inclusion. Results A total of 108 patients who received RRT were included in the study. The most common reasons for initiation of RRT were a high/rising creatinine, high/rising urea, acidosis and fluid balance. The majority of the patients (79.6%; n=86) had three or more indications for RRT. A total of 353 intermittent haemodialysis/slow low-efficiency dialysis (IHD/SLED) sessions and 84 continuous renal replacement therapy (CRRT) sessions were recorded. The median (interquartile range (IQR)) CRRT dose was 25.8 (19.1 - 28.8) mL/kg/h. The median (IQR) urea reduction ratio for IHD/SLED was 32.4% (15.0 - 49.8). Conclusion Patients in this study had multiple indications for initiating RRT. The dosing of RRT was not optimal, with a wide range shown in CRRT, and the majority of patients did not achieve a urea reduction ratio (URR) >65%. Contributions of the study Renal replacement therapy is a scarce resource in Africa. Little is known about the current types and dosing of RRT in critical care units in South Africa. We showed that critically ill patients had multiple indications for RRT and the dosing was not optimal.