The Importance Of Residual Kidney Function in Hemodialysis Patients

Contact: Audrey Hu Whatsapp/hp: 0086 13880143964 Email: audrey.hu@wecistanche.com

JESSICA KONG, et al

ABSTRACT: In contrast to peritoneal dialysis, residual kidney function (RKF) is commonly disregarded for hemodialysis (HD) patients and is not regularly monitored or taken into account in routine clinical care. This is despite evidence that higher levels of RKF in HD patients are associated with better outcomes, including survival, total solute clearance, nutrition, inflammation, and fluid balance. This review aims to summarise the clinical effects of RKF specifically in HD patients. Some level of RKF (residual kidney function) is present in over 80% of patients at the time of dialysis initiation, and while this declines over time, up to 30% of patients on HD for 5 years still have a measurable level of native kidney function. There is little evidence on how best to preserve RKF in HD patients, although it has been observed that intensive HD regimens in incident HD patients appear to accelerate RKF decline. RKF (residual kidney function) is not commonly factored into HD prescription and measures of adequacy, despite the fact that some guidelines such as Kidney Disease Outcomes Quality Initiative (KDOQI) and European Best Practice Guidelines suggest that it is reasonable to do so. This likely relates, at least in part, to perceived concerns regarding the inconvenience of timed urine collections and to the complexity and lack of consensus regarding the methods for integrating the intermittent clearance of HD with the continuous clearance of native renal function. Further research is required into how best to maintain and maximize the benefits of RKF in HD patients.

KEYWORDS: end-stage renal failure, hemodialysis, incremental hemodialysis, residual kidney function.

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Residual kidney function (RKF) in dialysis patients is defined by the remaining ability of the diseased kidneys to excrete water and uraemic solutes. In contrast to peritoneal dialysis (PD), in hemodialysis (HD) practice, RKF (residual kidney function) is not commonly measured or taken into account when determining clinical care or dialysis prescription. This is despite higher RKF correlating with better outcomes, such as improved survival, solute clearance, nutrition,1 anemia, and phosphate control,² suggestings that efforts for monitoring and preserving RKF in HD patients may be worthwhile (Table 1). Both the Kidney Disease Outcomes Quality Initiative (KDOQI)3 and European Best Practice Guidelines (EBPG)4 have suggested that RKF may be incorporated into the HD prescription, so-called incremental HD, but this is not broadly practiced due to uncertainties about how this can be effectively and safely achieved.

The primary purpose of this review is to summarise the current literature about the relationships between RKF (residual kidney function) and outcomes specifically in the HD population. Furthermore, we aim to discuss the methodology for RKF measurement and to briefly discuss how RKF (residual kidney function) might be taken into account in the consideration of HD dosing.

METHOD

Literature was obtained by searching the Ovid MEDLINE and EMBASE databases between 15 August 2017 and 01 March 2018. The search terms used were 'chronic kidney failure', 'hemodialysis', 'residual renal function', 'residual kidney function', and 'incremental'. A total of 650 articles were obtained. Non-English articles, duplicates, and articles without an abstract were then excluded. Additional articles were manually sourced from reference lists of relevant retrieved articles. Articles were included if their primary focus was on RKF (residual kidney function) in the HD patient population and incremental HD.

RKF (residual kidney function) AND PATIENT SURVIVAL

The importance of RKF (residual kidney function) has been demonstrated in multiple studies of PD, but evidence related to its benefits in HD has only been emerging recently. Regarding PD data, a reanalysis of the Canada-United States Peritoneal Dialysis (CANUSA) study showed a significant contribution of RKF (residual kidney function) in 601 end-stage kidney disease patients who were involved in this multicentre, prospective cohort study.⁵ There was a 12% decrease in the relative risk (RR) of death with each 5 L/week per 1.73 m2 increment in glomerular filtration rate (GFR) and a 36% decrease in RR of death with each 250 mL increase in urine volume. In contrast, peritoneal clearance was not shown to be associated with patient survival.

Multiple studies have tried to examine if this association may extend to HD patients. In the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) study, 740 incident HD patients were followed over a median follow-up time of 1.7 years, and patient survival in relation to RKF (residual kidney function) was investigated.⁶ Mortality was 56% lower with each 1.0 unit increase in renal urea standard Kt/V/week (RR 0.44; 95% CI, 0.30–0.65, P < 0.0001).

The Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) study followed 734 incident HD patients for a year and found similar results. In this study, RKF was defined as patient-reported urine output (UO) of at least 250 mL daily. Preserved RKF (residual kidney function) at 1 year was independently associated with 30% lower all-cause mortality (HR 0.7, CI 0.52–0.93, P = 0.02), even after adjustment for confounders including demographics and clinical characteristics.⁷

Furthermore, a prospective observational cohort study by Shemin et al. found that the presence of RKF (residual kidney function), even at a low level, was beneficial. In this study, after adjustment for other factors, RKF was protective against mortality over a 2-year period (odds ratio (OR) 0.44; 95% CI 0.24–0.81, P = 0.008).⁸ The mechanisms through which the persistence of RKF may contribute to improved survival are likely to be multifactorial and are outlined below and in Table 1.

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EFFECT OF RKF (residual kidney function) ON SOLUTE CLEARANCE

In contrast to the intermittent clearance of solutes provided by HD, native renal function is continuous, and this may explain the benefits conferred by RKF in end-stage kidney disease patients. Kt/Vurea, dialyzer urea clearance adjusted for volume of distribution, is often used as a marker of dialysis adequacy. A native residual renal urea clearance (KRU) of 3 mL/min in an average patient is equivalent to a weekly standard Kt/Vurea of approximately 1.0.³

Fry et al. proposed that the benefits associated with RKF (residual kidney function) are not only due to the enhanced clearance of small molecular weight solutes, such as urea and creatinine but also due to that of larger uraemic toxins, such as middle molecular weight molecules, which are poorly cleared by HD.⁹ In a cross-sectional, retrospective, observational study involving 297 patients, beta-2 microglobulin (β2M) was used as a representative middle molecule. This study found that RKF is associated with better clearance of β2M. Patients with KRU < 0.5 mL/min had significantly higher β2M levels than those with KRU of 0.5–1 mL/min (28.2+-6.2 vs 23.1+-4.6 mg/L, P < 0.001), suggesting that even low levels of RKF may be beneficial. Similar results were reported in another study where patients with RKF were found to have significantly lower levels of β2M.¹⁰

RKF (residual kidney function) AND FLUID BALANCE Cardiovascular disease is known to be a leading cause of mortality in HD patients. Important determinants include accelerated atherosclerosis and left ventricular hypertrophy (LVH). Both volume overload and increase of total peripheral vascular resistance in HD patients contribute to LVH. The presence of RKF (residual kidney function) may improve fluid balance and thus provide cardiovascular benefits.

Previous cross-sectional studies conducted in PD patients have shown that decline in RKF (residual kidney function) was independently associated with increased left ventricular mass index¹¹ as well as poor blood pressure control.¹² In HD patients, RKF (residual kidney function) contributes to enhanced capacity for sodium removal and volume control, indicated by reduced inter-dialytic weight gain.¹³ A significantly lower ultrafiltration requirement was also noted in patients with KRU ≥ 1 mL/min per 1.73 m2. ¹⁴ A cross-sectional observational study of 59 maintenance HD patients evaluated the cardiac effects of RKF, defined by having 24-h UO > 200 mL.¹⁵ This study found that LVH and left ventricular systolic dysfunction were less severe in patients with RKF compared with those without RKF, hypothesized to be related to better fluid balance and blood pressure control conferred by RKF.

This contrasts with results from a prospective study, which suggested that the persistence of RKF (residual kidney function) was largely dependent on volume overload.16 Volume status was assessed by cardiothoracic index and left ventricular chamber size on echocardiographic examination. Strict volume control was applied to 19 incident HD patients for 3 months. It was found that the left ventricular mass index decreased by 36% during this period, indicating regression of LVH, while a dramatic decrease in RKF was also noted, suggesting that preservation of RKF might contribute to volume overload and LVH. The power of the study is, however, limited by its small sample size and short duration of study. Nonetheless, this study highlights that chronic hypervolemia as a method of preserving RKF should be avoided. Of note, studies in patients on PD have found that extracellular volume expansion does not help preserve RKF,^17,18 whereas volume depletion can, as would be expected, negatively impact RKF.¹⁹

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RKF (residual kidney function) AND INFLAMMATION

Chronic, low-grade inflammation is common in chronic dialysis patients, although the exact underlying mechanisms are not fully understood. Part of the increased inflammatory response may be related to platelet contact activation and complement cascade activation from blood flowing through the extracorporeal circuit, resulting in the release of a range of different pro-inflammatory cytokines. A cross-sectional observational study by de Sequera et al. found that higher RKF (residual kidney function) was associated with lower levels of inflammatory parameters.10 A lower percentage of CD14 +/CD16++ inflammatory monocytes (14.6% vs 28.3%, P = 0.02) and lower concentrations of C-reactive protein (CRP) (6.2 vs 21.4 mg/L, P = 0.038) were found in patients with KRU >1 mL/min and diuresis >100 mL/day. Activated CD16+ monocytes induce endothelial damage, which may contribute to the development of atherosclerosis. Shafi et al. also observed a similar association between RKF and lower levels of inflammatory markers CRP and interleukin (IL)-6.7 Similarly, Yang et al. observed higher UO in HD patients correlated with lower levels of high-sensitivity CRP.²⁰

RKF (residual kidney function) AND NUTRITIONAL STATUS

In a retrospective study of 650 incident HD patients, RKF (residual kidney function) was shown to be associated with better nutritional status.¹⁴ Compared with patients with KRU <1 mL/min per 1.73 m2, those with KRU ≥ 1 mL/min per 1.73 m2 had higher serum albumin and normalized protein catabolic rate (nPCR) for up to 36 months. A cross-sectional multicentre study conducted in Taipei with 704 maintenance HD patients also found results that suggest RKF (residual kidney function) contributes to improved nutritional status in HD patients, with a 1-liter increase in residual 24-h urine volume associated with a 1.4 g/L increase in serum albumin.²⁰

RKF AND RENAL ANAEMIA

Observational studies have found a requirement for a reduced erythropoietin (EPO)-stimulating agent in patients with significant RKF (residual kidney function). Vilar et al. found reduced weekly EPO dose and reduced EPO resistance index for up to 48 months after HD initiation in patients with KRU ≥ 1 mL/min per 1.73 m2, although no significant difference in serum hemoglobin was noted.¹⁴

The CHOICE study also showed that patients with daily UO > 250 mL at 1 year after commencing HD required a lower dose of EPO compared with those without (P = 0.001).7 Similar trends were noted with the EPO resistance index.

RKF AND PHOSPHATE BALANCE

Hyperphosphataemia is associated with vascular calcification and cardiovascular mortality among dialysis patients. Iwasawa et al. investigated if RKF (residual kidney function) contributes significantly to phosphate elimination, performing a retrospective, cross-sectional study with 79 chronic HD patients being categorized into two groups: 35 patients with GFR ≥ 3 mL/min and 44 patients with GFR <3 mL/min.21 Phosphate removed by dialysis was assessed in nine anuric patients. A linear association was observed between residual GFR and urinary phosphate excretion. Patients with GFR ≥ 3 mL/min had approximately double mean weekly phosphate removal (2000.3+-804.1 mg) compared with the amount of phosphate removed in a single HD session (1019.9+-300 mg) (P < 0.001). In contrast, patients with GFR < 3 mL/min (952.9 +- 418.8 mg) had similar mean weekly phosphate removal compared with that removed by a single HD session.

Another cross-sectional study conducted in China found similar results.²² RKF (residual kidney function) was found to be associated with a significant capacity to excrete phosphate. Weekly phosphate excretion by urine in patients with RKF (daily UO > 200 mL) was found to range from 300 to 1500 mg, which was equivalent to the total removal of by a single 4-h HD session. This was also significantly higher than patients with daily UO ≤ 200 mL (769+-318 vs 122+-106 mg/week, P < 0.001). This corresponded to lower requirements for phosphate binding medication (CaCO3) in these patients. Interestingly, anuric patients with higher predialysis serum phosphate concentration had lower phosphate removed by one HD session compared with those with RKF. The underlying mechanisms and the kinetics of phosphate during HD, however, are not fully understood yet. This study is similarly limited by the inability to accurately record patients’ dietary phosphate intake as well as its small sample size.

RKF AND VASCULAR DISEASE

Vascular disease is another common complication that contributes to significant cardiovascular morbidity in HD patients, but few studies have examined the relationship between RKF (residual kidney function) and vascular calcification and atherosclerosis. Most recently, a cross-sectional observational study set out to examine the relationship between RKF and atherosclerosis²³ in a study of 39 PD patients and 53 HD patients who were on maintenance dialysis therapy for at least 3 months to up to 3 years. In this study, atherosclerosis was defined as >10 mm carotid artery intima media thickness and/or the presence of plaque detected by B-mode ultrasonography. RKF was measured as GFR derived from inter-dialytic urine collection. In both univariate and multivariate analysis, higher RKF (residual kidney function) predicted a lower risk of atherosclerosis (OR 0.95; 95% CI 0.54–0.99, P = 0.041). However, this analysis was not specific to HD patients.

Another cross-sectional study conducted in China reported an association between a loss of RKF (residual kidney function) and abdominal aortic calcification (ACC).²⁴ In this study, loss of RKF was defined as daily UO < 200 mL, and abdominal ACC score was measured based on lateral lumbar radiographs. Loss of RKF was associated with a higher calcification score, with a beta of 0.22 (95% CI 0.08–0.53, P = 0.01), as analyzed by multivariable linear regression. This association was independent of identified confounders of vascular calcification such as age, HD vintage, diabetes, CRP, and calcium-phosphorus product.

RKF AND QUALITY OF LIFE (Q_OL)

RKF (residual kidney function) has been associated with a better QoL in PD patients.²⁵The mechanisms are uncertain but could be related to improved nutrition, fluid balance, anemia, and phosphate control. In the CHOICE study, HD patients with UO at baseline also reported overall better QoL (P = 0.05) as assessed by a validated patient self-reporting questionnaire.⁷ However, data related to specific symptom burden in relation to RFK are generally lacking in the HD patient population.

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RKF MEASUREMENT

There is debate regarding the best way of measuring RKF (residual kidney function). Renal function is most commonly measured as GFR. The ideal method for measuring RKF is one that is accurate, reproducible, cost-effective, and simple to perform. At present, none of the available options perfectly fulfill these criteria, such that the choice of the methodology involves some compromises between accuracy, convenience, and cost. Direct methods such as inulin, 51chromium ethylenediaminetetraacetic acid (EDTA), and iothalamate radiocontrast clearance are considered the most accurate way of determining GFR but have limited place in the routine monitoring of RKF and have not been adequately studied for this purpose.

Currently, RKF is most commonly measured by a timed urine collection for urea and creatinine clearance.³ This is ideally performed over the whole inter-dialytic period, typically 44 h for a thrice-weekly regimen, to reduce the effect of variation in GFR across the inter-dialytic period. An alternative approach is a 24-h urine collection, which may be more convenient for patients. A complicating factor when measuring RKF (residual kidney function) by timed urine collection in HD patients, compared with PD patients, is the fluctuating urea and creatinine levels across the interdialytic time period. To deal with this, the recommended method is to use the mean values of plasma measurements taken at the beginning and end of the timed urine collection.⁴

Renal urea clearance underestimates GFR due to tubular reabsorption, while creatinine clearance overestimates GFR due to tubular secretion. The mean of the urea and creatinine clearances has been shown to correlate well with inulin clearance.²⁶ For this reason, EBPG guidelines recommend measuring RKF (residual kidney function) in HD patients as the residual GFR, determined as the mean of urea and creatinine clearances.⁴ This composite clearance, however, does not accurately account for tubular function or clearance of protein-bound solutes and middle molecular weight molecules. In contrast, the KDOQI guidelines advise measuring RKF by urea clearance (KRU),³ which has the potential disadvantage of underestimating GFR but reduces the risk of overestimating GFR and helps facilitate the integration of RKF with dialysis clearance, which by convention is based on urea kinetics.

Recent studies have also considered other methods of measuring RKF (residual kidney function) on a regular basis, including measurement of novel serum biomarkers such as cystatin C, beta 2 microglobulins (β2M), and beta-trace protein. The primary advantage of this approach is avoidance of the need for timed urine collections. Wong et al. demonstrated that serum β2M is independently associated with only RKF and diabetic status but not with dialysis parameters including Kt/V, and could potentially be used as a marker for RKF.27 In this study, equations were derived from serum β2M and betatrace protein to predict GFR and KRU, and these equations were then tested in a validation cohort, comparing the calculated values with measured KRU and GFR (calculated from the mean of urinary urea and creatinine clearances). Patients with KRU > 2 mL/min were correctly identified in 90% of cases. A prediction equation for GFR that includes both beta-trace protein and β2M provided a better estimate than either alone. Hypothetically, if this method was used to identify patients with sufficient RKF to allow adjustment of HD dose, more than 95% of patients would receive a dialysis dose at or above the target set by KDOQI guidelines, but 5% of patients would be under-dialyzed. A limitation of the study was that biomarkers were also only measured at a single time point, and hence, the rate of change of these markers relative to the progressive decline of RKF was not studied. In addition, β2M levels may also be affected by comorbidities and other clinical factors that are not fully understood. Estimation of RKF using plasma beta-trace protein might also be less accurate in patients undergoing haemodiafiltration, which has been reported to reduce betatrace protein levels by 61%.²⁸

Trend and prevalence of RKF

RKF (residual kidney function) have been reported to be better maintained in PD patients than in HD patients.¹⁹ Jansen et al. found that, after adjustment for baseline variables and dropout, PD patients were shown to have 30% higher GFR than HD patients (P < 0.0001) at 1 year after the start of treatment. The most pronounced rate of decline in GFR occurred in the first 3 months after the start of treatment. In contrast, however, Mckane et al. found no difference in the rate of decline of KRU between patients receiving high-flux biocompatible HD and those receiving continuous ambulatory PD.²⁹ The more rapid decline of KRU was noted in the first 12 months after dialysis initiation. Whilst RKF declines following dialysis initiation, it is maintained in some patients. A UK study of 650 incident HD patients found that 58.1% and 31% of patients had a KRU ≥ 1 mL/min per 1.73 m2 at 2 and 5 years after HD initiation, respectively.14 Little is known about incidents and prevalent RKF in most HD populations, with registries such as ANZDATA not collecting data on this.

Clinical strategies for the preservation of RKF

In general, factors influencing the rate of RKF (residual kidney function) loss are less well studied and understood in HD, as compared with PD. Relevant variables potentially affecting the rate of decline of RKF in HD patients are summarized in Table 2 and include demographic factors and comorbidities. Evidence regarding clinical strategies for the preservation of RKF in HD is limited, although there is some evidence that RKF loss can be influenced by the aspects of the HD prescription, including the intensity and frequency of the HD regimen (Table 2).^30,31Avoidance of intra-dialytic hypotension may also help pre-serve RKF.19,³¹ In failed renal transplant patients, maintenance of immunosuppression is associated with better preservation of RKF (residual kidney function); in PD patients,³² however, data are not available on this in HD patients. The use of ultrapure dialysis fluid has been reported to slow the loss of RKF (residual kidney function) in HD patients.³³ Avoidance of nephrotoxins such as radiocontrast dye, non-steroidal anti-inflammatory drugs, and aminoglycosides are advised,³⁴ although direct data on this are lacking.

Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers has been demonstrated in several randomized controlled trials to help preserve RKF (residual kidney function) in PD patients.³⁵ However, while there is some observational evidence that the use of these agents is associated with the preservation of RKF in HD patients, the only prospective randomized controlled trial performed in HD patients found that irbesartan treatment for 1 year did not affect the decline in GFR or urine volume.³⁶

Incremental HD

It remains uncommon in current practice to take RKF (residual kidney function) into account when determining HD prescription and adequacy. This contrasts with PD, where RKF is routinely measured and systematically contributes to measures of treatment adequacy. Incorporation of RKF into HD prescription has been promoted by some investigators, so-called incremental HD, whereby patients with more RKF do less HD, whereas patients lacking RKF do more HD. Notably, both K-DOQI and EBPG guidelines support the use of Incremental HD prescription provided careful monitoring of RKF is performed. In contrast, there are no current KHA-CARI guidelines for HD adequacy, and previous versions of those guidelines did not address a role for RKF. Specifically, the KDOQI guideline suggested that, for HD patients with KRU ≥ 2 mL/min per 1.73 m2, the dose of HD may be reduced provided RKF is measured periodically to avoid inadequate dialysis.3 Similarly, the EBPG recommends measuring RKF in HD patients using the mean of urea and creatinine clearances to estimate residual GFR and offer suggestions to incorporate this into the HD prescription to allow individual adjustment of dialysis prescription to meet minimum dialysis adequacy target.⁴

Effect of HD on RKF

One concern that has been raised is that more intensive HD regimens might better accelerate the loss of RKF (residual kidney function). Data from the Frequent Hemodialysis Network (FHN) trials showed that more frequent nocturnal HD of six times per week accelerates the loss of RKF, compared with the standard three times per week HD.³⁰ In the FHN nocturnal study, 52 and 67% of patients receiving frequent nocturnal HD have zero urine volume at months 4 and 12, compared with 18 and 36%, respectively, in the conventional HD group. This association was not found in the FHN frequent daily HD study, where patients had a lower baseline RKF (residual kidney function).

Obi et al. also compared the changes in renal urea clearance and urine volume between patients initiated on conventional thrice-weekly HD regimen and those initiated on incremental twice-weekly HD regimen for >6 continuous weeks.37 A total of 351 incremental HD patients were matched to 8068 conventional HD patients. From month 3 onwards up to month 15, patients who were initiated on a twice-weekly regimen had 16% higher renal urea clearance (95% CI, 5–28%) than those who received a thrice-weekly dialysis regimen. In this study, increased mortality was observed in patients doing twice a week HD with a KRU ≤ 3.0 mL/min per 1.73 m2, but it was not different for those with KRU > 3.0 mL/min per 1.73 m2.

Similar results have been found in a retrospective Chinese study involving 85 incident HD patients with UO ≥ 500 mL/ day at baseline.31 A total of 30 patients were initiated with twice-weekly HD for 6 months or longer, and 55 patients were started and maintained on thrice-weekly HD treatment. The selection of patients for twice-weekly HD was not random and was determined based on clinical condition, patient choice, compliance, and economic conditions. Compared with the thrice-weekly group, the twice-weekly HD group was shown to have a lower RKF (residual kidney function) loss (10% vs. 40%, P = 0.03), especially in the first year of HD initiation.

Intra-dialytic hypotension has been hypothesized to be a possible cause of accelerated loss of RKF (residual kidney function), with transient drops in blood pressure during dialysis causing ischaemic injury to kidneys. In a prospective observational study conducted in Taiwan, twice-weekly HD was associated with a slower decline in RKF as indicated by urine volume and creatinine clearance, which was consistent with results from other studies. In addition, significantly fewer intra-dialytic hypotensive episodes were observed in the twice-weekly HD group compared with the thrice-weekly HD group (0.26+-0.49 times/month vs 1.10+-1.21 times/month; P < 0.001).³⁸

Methodology and safety of incorporating RKF into the HD prescription

To include RKF into the HD prescription for an incremental HD approach, RKF (residual kidney function) clearance needs to be added to dialyzer clearance to calculate the total clearance. However, because HD is intermittent while RKF is continuous, either RKF needs to be converted to an equivalent intermittent clearance or dialysis clearance needs to be converted to an equivalent continuous clearance. Multiple approaches have been proposed, but there is yet to be a universally accepted consensus as to the best method. Options include converting the weekly dialysis clearance into the equivalent renal urea clearance (EKRc),39 use of the (weekly) standard Kt/V40, and converting RKF to the equivalent intermittent clearance (Kt/V).14 Details of these methods are beyond the scope of this review, and readers are referred to the primary references and other reviews.

A potential concern with incremental HD is a higher risk of poor outcomes related to inadequate HD. This concern relates to real-world questions about the reliability of methods for monitoring RKF (residual kidney function), the need for patients to comply with timed urine collections, and the need for physicians to proactively increase the HD dose when RKF declines. There are no large randomized trials comparing incremental HD to a standard HD prescription.

Vilar et al. reported the outcomes of 650 incident patients managed in an incremental high-flux HD program over a 15-year period.14 A key finding was that better outcomes were seen in patients with KRU ≥ 1 mL/min per 1.73 m2, despite these patients being treated with a lower dose of HD. While this provides some reassurance for the safety of incremental HD, the lack of a control group for the study limits its generalizability.

Zhang et al. also found no difference in clinical outcome in terms of HD adequacy, biochemical measures, cardiovascular morbidity, or hospitalization rates between twice-weekly and thrice-weekly HD groups.³¹ However, the power of this study is limited by its small sample size of 85 incident HD patients.

Obi et al. examined the relationship between the incremental dialysis regimen and mortality risk.37 In survival analyses after 1 year, there was no difference in all-cause mortality risk associated with incremental HD compared with conventional HD. Subgroup analyses, however, revealed 61% higher mortality risk in patients with a lower baseline KRU of <3 mL/min per 1.73 m2 (HR 1.61, 95% CI 1.07–2.44) but not in those with KRU > 3 mL/min per 1.73 m2 (HR 0.99, 95% CI 0.76–1.28). Limitations of this study include selection bias as patients who have lower KRU and higher comorbidity burden were less likely to be prescribed an incremental regimen. In addition, the sample size of patients receiving the incremental regimen was relatively small, resulting in a wide confidence interval for the estimate. Nonetheless, this study underscores the potential risks of twice-weekly dialysis in patients with minimal RKF (residual kidney function). This is consistent with other studies showing increased mortality with twice-weekly dialysis when RKF (residual kidney function) is not incorporated into the prescription.⁴¹

Concerning results were shown in a prospective, multicentre observational study by Hwang et al. 42 They found an increased risk of mortality (HR 4.2; 95% CI, 1.02–17.32, P = 0.04) in patients with RKF undergoing twice-weekly HD (n = 113) compared with those with RKF (residual kidney function) undergoing thrice-weekly HD (n = 137), despite adequate dialysis dose and fluid control. The authors postulated that this was possibly related to the poorer nutrition (reduced normalized protein catabolic rate) observed in the twice-weekly group at 24 and 36 months and suggested that risk factors other than RKF should also be taken into account when prescribing twice-weekly HD.

In summary, there is substantial evidence suggesting that there are many benefits conferred by RKF (residual kidney function), such as improved fluid balance, nutritional status, and better clearance of solutes. Efforts to preserve RKF (residual kidney function) are justified, although how best to do this is unclear. Avoidance of nephrotoxins in HD patients with remaining RKF is advised. Some evidence suggests that more intensive HD regimens accelerate the loss of RKF (residual kidney function), so this should be taken into account, particularly around the time of HD initiation. Adjustment of HD prescription taking into account RKF (residual kidney function), incremental HD, may have advantages in terms of RKF preservation, quality of life, and health-care costs, which need to be balanced against the risks, including the dangers of inadequate dialysis. Further research is required into how to best preserve RKF in HD patients and to clarify the role of RKF (residual kidney function) in determining the optimal HD prescription.

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From: 'The importance of residual kidney function in hemodialysis patients' by JESSICA KONG, et al

--- Nephrology 23 (2018) 1073–1080

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