The contribution of residual renal function to overall nutritional status in chronic haemodialysis patients

Takeshi Suda1, Kinya Hiroshige2, Takayuki Ohta1, Yujiro Watanabe1, Masako Iwamoto1, Kaori Kanegae1, Akira Ohtani2 and Yasuhide Nakashima1

1 Second Department of Internal Medicine, School of Medicine, University of Environmental and Occupational Health, Fukuoka, Japan and 2 Renal Division, Social Insurance Chikuho Hospital, Fukuoka, Japan

Correspondence and offprint requests to: K. Hiroshige, MD, Renal Division, Social Insurance Chikuho Hospital, 765-1 Yamabe, Nougata City, 822-0034 Fukuoka, Japan.



   Abstract
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. The benefits of residual renal function (RRF) in peritoneal dialysis patients have been described frequently. However, previous reports have shown that RRF diminished faster in haemodialysis (HD) patients than in peritoneal dialysis patients, and in most of the studies in HD patients, RRF was ignored. In this study, the RRF in chronic HD patients was studied to assess its impact on patients' nutritional status.

Methods. In 41 chronic HD patients with at least a 2-year history of HD treatment, RRF was determined by a urine collection for 7 consecutive days. Nutritional parameters, such as percentage body fat, fat-free mass index, serum albumin concentration and normalized protein catabolic rate, were also measured.

Results. In all 41 patients, mean weekly total Kt/V urea was 4.88 and renal Kt/V urea was 0.65. RRF was well correlated with serum albumin concentration, but dialysis Kt/V urea was not. One year after the start of this study, RRF and nutritional indices were re-examined and patients were classified into two groups: with RRF, preserved residual renal diuresis over 200 ml/day (mean, 720 ml; range, 230–1640 ml), N=23; and without RRF, persistent anuria (mean, 51 ml; range, 0–190 ml), N=18. At the start of this study, the mean serum albumin concentration and mean normalized protein catabolic rate in patients with RRF were 3.84 g/dl and 1.16 g/kg/day, respectively, which were significantly higher than those in patients without RRF (P=0.02 and P=0.0002, respectively), despite total (renal+dialysis) Kt/V urea being equal in both groups. During the 1-year study period, there was no significant change in total Kt/V urea in either group. Mean serum albumin concentration increased to 4.05 g/dl in patients with RRF, but did not change significantly (from 3.66 to 3.62 g/dl) in patients without RRF. The same trend was observed in all other parameters.

Conclusion. Over half of our HD patients had sufficient RRF. RRF itself may have a beneficial effect on nutritional parameters, and it is important to determine RRF over time, even in chronic HD patients.

Keywords: albumin; dialysis efficacy; haemodialysis; nutrition; residual renal function



   Introduction
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Malnutrition, which is frequently present in haemodialysis (HD) patients, may be a consequence of multiple factors including disturbances in protein and energy metabolism, hormonal derangements and poor food intake because of anorexia [1,2]. It is also generally accepted that nutritional status is related to the amount of dialysis delivered, and low dialysis efficacy is associated with higher rates of morbidity and mortality [35]. Residual renal function (RRF), which is better preserved in continuous ambulatory peritoneal dialysis (CAPD) patients [6], produces a certain benefit for total dialysis efficacy and possibly leads to better nutritional status and outcome in patients. There are several reports indicating the impact of RRF on dialysis dose, the elimination of middle and large molecular substances and the nutritional status in CAPD patients [79]. An international, cross-sectional, multicentre study showed that loss of renal function is associated with anorexia and symptoms of severe malnutrition in CAPD patients [10].

Additive effects of renal solute and fluid elimination and metabolic function in the remnant kidney may greatly benefit nutritional status and quality of life, even in patients receiving chronic HD. However, to our knowledge there are no available data concerning the impact of RRF on the nutritional status in chronic HD patients and RRF has been ignored in most of the large-scale epidemiological studies on HD patients. In our centre, we collected a urine sample from patients for a week the beginning of the study and 12 months later; we found that a considerable number of patients who had received dialysis treatment for over 2 years maintained a significant residual renal diuresis. We then calculated total weekly dialysis dose including RRF and examined its correlation to overall nutritional status. We also examined whether patients with significant RRF during the 1-year study period had better and improved nutritional status than patients without RRF.



   Subjects and methods
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 Subjects and methods
 Results
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Patients
In our centre, over 100 patients were receiving HD treatment simultaneously. Thirty-six patients who had been admitted to our hospital at the start of this study were excluded because of less physical activity compared with outpatients. Sixteen patients with severe complications affecting exercise capacity, such as old cerebral infarction or myocardial infarction, were also excluded. Outpatients with evidence of an underlying disease, such as collagen disease, liver cirrhosis, malignancy or an endocrinological disorder (except diabetes mellitus) were excluded, as were patients undergoing major surgery during the study period. Thus, patients with factors unrelated to dialysis that may affect nutritional status were excluded. The remaining 41 stable patients undergoing maintenance HD for more than 2 years were included in this study.

All patients were maintained on thrice weekly 4-h chronic HD treatment at the Dialysis Center of Chikuho Hospital, using bicarbonate as a buffer solution. Haemodialysers used during the experimental period included polysulfone (PS, Fresenius, Bad Homburg, Germany) sterilized by autoclave and polyacylate/polyethylsulfone (PEPA, Nikkiso Co., Tokyo, Japan) sterilized by gamma irradiation. Patients' demographic characteristics are described in Table 1Go. Informed consent was obtained from all patients, and the study was conducted in accordance with the principles of the Declaration of Helsinki.


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Table 1. Patient characteristics and residual renal function (RRF) and biochemical measures
 
Study protocol
At the start, RRF and nutritional assessments were evaluated and arterial blood bicarbonate concentration, plasma C-terminal parathyroid hormone (c-PTH), ß2-microglobulin, potassium and inorganic phosphate concentrations were measured in all patients. Daily urine collection for 7 consecutive days was used to evaluate RRF. RRF was estimated by calculating glomerular filtration rate (GFR) expressed as a mean of creatinine and urea clearance (ml/min/1.73 m2). We also calculated the dialysis Kt/V urea and renal Kt/V urea separately. We then examined the impact of RRF on the total Kt/V urea, which was determined by the sum of renal and dialysis values and was expressed as a weekly value. Correlations between RRF or dialysis efficacy and nutritional parameters were also examined.

Total dialysis dose including RRF and nutritional parameters was evaluated again 1 year after the start of this study. All patients were divided into two groups simply by urine volume. A group of 23 patients with significant RRF had weekly diuresis over 1400 ml both at the start and the end of this study. The remaining 18 patients were anuric and were categorized as being without RRF. We examined the differences between both groups in terms of biochemical parameters, nutritional status, total Kt/V urea and their changes after 1 year.

Nutritional parameters and urea kinetics
Nutritional assessment consisted of serum albumin concentration and anthropometric measurements. Blood samples were collected just before the first dialysis session in a week and plasma albumin, potassium and inorganic phosphate concentrations were measured using a routine method. Bicarbonate concentration in arterial blood was measured using an autoanalyser and plasma c-PTH and ß2-microglobulin concentrations were measured by radioimmunoassay.

Height was measured and body dry weight (kg) was determined by clinical manifestations and chest X-ray. Anthropometric measurements were made on triceps and subscapular skinfold thickness by the same observer, who was unaware of the group status of patients. All measurements, including body dry weight, were taken after a dialysis session to minimize any distortion caused by excess tissue fluid. Body fat percentage (%fat) was calculated using triceps and subscapular skinfold thickness based on the Brozek's equation [11]. Lean body mass (LBM, kg) was calculated using these values and dry body weight and was expressed as a fat-free mass index (LBM/height2).

Blood samples for urea nitrogen were drawn before and after the first weekly dialysis session and before the next session. The normalized protein catabolic rate (nPCR, g/kg BW/day) was calculated according to the equation of Gotch and Sargent [4], and dialytic Kt/V urea was calculated according to Daugirdas's equation [12].

Statistical analysis
All the data are expressed as mean±SD, unless indicated otherwise. The differences of paired and unpaired observations between the two groups were analysed using Wilcoxon and Mann–Whitney tests, respectively. A comparison of discrete variables in different groups was made using Fisher's exact test. Correlations between variables were established by Pearson correlation coefficient. Differences were considered significant at P<0.05.



   Results
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 Subjects and methods
 Results
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At the start of this study, mean daily urine volume was over 400 ml/day and mean estimated creatinine clearance (Ccr) was near 1.0 ml/min in all patients; mean dialysis duration was >3 years (Table 1Go). Total weekly Kt/V urea and renal Kt/V urea was 4.88 and 0.65, respectively; at the start, in all patients, RRF affected total solute elimination by over 10%. Renal Kt/V urea was well correlated with serum albumin concentrations (r=0.44, P=0.0056), however, dialysis Kt/V urea was not correlated with serum albumin. Neither renal Kt/V urea nor dialysis Kt/V urea correlated with anthropometric measurements such as %fat and fat-free mass index (data not shown).

Although there were no significant differences in age, sex, duration of dialysis, primary renal disease, body weight gain between dialysis sessions, and predialysis serum concentrations of potassium and inorganic phosphate between groups with and without RRF, 23 patients had better residual renal diuresis and showed a favourable value even at 1 year after the start of this study (Table 1Go). Patients with RRF had much higher mean calculated Ccr (2.12 ml/min), which decreased to 1.71 ml/min after 1 year, although the decrease was not statistically significant. A significantly higher level of bicarbonate in arterial blood and significantly lower levels of plasma c-PTH and ß2-microglobulin were measured in patients with RRF.

Total urea elimination dose manifested by total Kt/V is shown separately for dialysis and renal Kt/V urea in Table 2Go and Figure 1Go. Patients with RRF had a significantly higher renal Kt/V urea of 1.099, however, total weekly Kt/V urea was 4.9 in both groups at the start of this study. One year later, significant residual renal diuresis persisted, with a renal Kt/V urea of 0.903 in patients with RRF, and the total weekly Kt/V urea was 4.8. In patients without RRF, a slight decrease in weekly dialysis Kt/V urea resulted in a decrease in total Kt/V urea to 4.4, although this decrease was not statistically significant. No difference in total Kt/V urea was observed between the groups.


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Table 2. Nutritional parameters and weekly Kt/V urea at the start and the end of the study
 


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Fig. 1. Weekly renal Kt/V urea and dialysis Kt/V urea in all patients (left), patients without residual renal function (RRF, centre) and patients with RRF (right). Patients with RRF showed a daily urine volume >200 ml both at the start and the end of this 1-year study. Weekly total Kt/V urea (renal+dialysis) was almost the same in patients with and without RRF.

 
The data for nutritional parameters in both groups are shown in Table 2Go and Figure 2Go. At the start, a significantly higher plasma albumin concentration of 3.84 g/dl was observed in patients with RRF compared with 3.66 g/dl in patients without RRF. Also, %fat and fat-free mass index tended to be higher in patients with RRF, although the difference was not statistically significant. Patients with RRF had a significantly higher total normal protein catabolic rate (nPCR) at the start, and nPCR increased only in patients with RRF. After 1 year, serum albumin concentration decreased slightly in patients without RRF, and the value in patients with RRF increased to 4.05 g/dl (P<0.0008, compared with that in patients without RRF). The same trend was observed when estimating %fat and fat-free mass index, and significant differences were observed at the end of this study.



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Fig. 2. Nutritional parameters in patients with and without residual renal function (RRF). Plasma albumin concentration and total (renal+dialysis) normalized protein catabolic rate (nPCR) were significantly greater in patients with RRF at the start of this study. During the 1-year study period, all parameters increased in patients with preserved RRF, but decreased slightly in anuric patients. At the end of this study, all parameters were significantly greater in patients with RRF.

 
The relationship between weekly total Kt/V urea and weekly total nPCR at the start of this study is shown in Figure 3Go. A positive, but weak, linear correlation was observed in both groups, and the increase in nPCR relating to the same increase in Kt/V urea was greater in patients with RRF.



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Fig. 3. The relationship between weekly total (renal+dialysis) Kt/V urea and total normalized protein catabolic rate (nPCR). In both groups, a significant positive linear correlation was observed; however, the increase in nPCR relating to the same increase in Kt/V urea was greater in patients with RRF.

 


   Discussion
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
In general, RRF diminishes faster in HD patients than in CAPD patients, although our previous study showed that the speed of decline in RRF on other peritoneal dialysis modalities, such as CCPD and NIPD, was as fast as that on HD [13]. Therefore, physicians can easily ignore the RRF in patients undergoing HD for more than 2 years, and the clinical relevance of RRF has been evaluated primarily in a CAPD population. The impact of RRF on dialysis performance is important in CAPD; a residual urea clearance of only 1 ml/min increases overall weekly clearance by 14–20% [7,14]. Therefore, RRF affects the daily determination of the number and volume of bags prescribed for each CAPD patient. However, our study documented that in all of our chronic HD patients, weekly renal Kt/V urea increased the weekly total Kt/V urea by over 10%; more than half of these patients had daily diuresis with a mean volume of 720 ml and corrected Ccr with a mean value of 2.12 ml/min. After 1 year, RRF was entirely maintained in most of our patients. RRF should be examined when estimating dialysis efficacy and nutritional status and should not be ignored even in chronic HD patients. However, in our anuric patients RRF did not significantly influence total dialysis dose (<2%). Only once anuria is confirmed by urine collection, can the impact of RRF on dialysis efficacy and nutritional status be ignored. Of course, it is also important to monitor the RRF over time. Nunan et al. [15] reported partial recovery of intrinsic renal function with a prolonged discontinuation of dialysis treatment in about 1% of their chronic HD patients.

At the start of this study, we observed a better correlation between RRF and serum albumin concentration and a tendency toward better nutritional status in patients with RRF. After 1 year, improvement of nutritional status was demonstrated in patients with RRF, but patients without RRF did not show any improvement, despite total Kt/V urea having been equal in both groups. Higher nPCR was observed in patients with RRF. A marked increase in body fat percentage was also observed in patients with RRF. These findings suggest the importance of RRF in protein and fat metabolism and oral food intake, assuming that nPCR reflects dietary protein intake in metabolically stable patients. These favourable changes may depend on RRF itself and not on total dialysis efficacy. Also, Scanziani et al. [16] reported that, despite total weekly clearance (Kt/V) being equal, severe malnutrition was observed in almost all CAPD patients without RRF. An increase in body fat percentage may indicate the improvement of energy malnutrition. An increase in energy intake might be an important factor contributing to better utilization of dietary protein leading to better nutritional status because metabolic studies indicate that the utilization of protein is greatly dependent on the energy intake and a low-energy intake reduces its utilization [17,18].

In HD patients, the contact of blood with bio-incompatible membranes, such as cuprophan, increases the production of interleukin (IL)-1, which stimulates muscle protein catabolism [19,20]. However, only biocompatible membranes were used in this study. Possible mechanisms for the contribution of RRF to increased nutritional status and estimated dietary protein intake are speculated as follows. First, mild acidaemia due to the greater acid elimination into urine may be a mechanism. Our patients with RRF had higher levels of plasma bicarbonate, but only with statistically weak significance. In acute renal failure, uraemic acidosis develops as GFR decreases and its magnitude may depend on the severity of renal failure [21], although there are no available data in chronic HD patients. Metabolic acidosis is associated with an increase in the catabolism of protein and essential amino acids and stimulates branched-chain amino acids (BCAA) catabolism, which leads to increased protein breakdown and decreased protein synthesis [22,23]. Preserved plasma BCAA levels may also contribute to increased appetite, based on a report showing that anorexia relates to decreased levels of BCAA in plasma [24]; Bergstrom [25] also emphasized the relationship between RRF and preserved appetite. Also, our patients with RRF had a higher estimated dietary protein intake, and this observation was consistent with that of Lopot et al. [26]. However, we cannot refer to this point specifically because we did not examine the plasma amino acid profile in this study. Metabolic acidosis also initiates a catabolic effect through a secondary mechanism, namely the increase in glucocorticoid production stimulated by acidosis [27].

A second mechanism may be better preservation of intrinsic renal function. If chronic HD patients have persistent RRF, they may also have better control of interdialysis fluid gain, better control of potassium and phosphorus serum levels and less dietary restriction [28]. Importantly, RRF may contribute to the removal of ß2-microglobulin and slow the progression of the devastating bone disease resulting from ß2-microglobulin-associated amyloidosis. The presence of intrinsic renal function also has beneficial effects on the maintenance of erythropoietin synthesis and conversion of vitamin D to its active form. Inhibiting the elevation of PTH may have a favourable anabolic effect by reducing amino acid release from muscle tissue [29]. All these factors have a beneficial effect on the quality of life, oral food intake, including energy intake, and protein metabolism in patients with RRF who receive chronic HD. In fact, significantly lower values of c-PTH and ß2-microglobulin in plasma were observed in our patients with RRF. However, in this study, there were no statistically significant differences in mean body weight gain and predialysis serum potassium and inorganic phosphate concentrations between groups, although these values tended to be higher in patients without RRF. No patient showed apparent bone or neural diseases associated with secondary amyloidosis, probably because mean dialysis duration was only 3 years. Also, we did not measure intact PTH, only c-PTH, which does not reflect biologically active PTH.

A third possible mechanism is the preservation of intrinsic renal metabolism of amino acids. If arginine production is preserved to some extent in remnant kidneys, increased levels of arginine are carried to skeletal muscle, which leads to an increase in protein synthesis [30]. Also, the kidneys play a role in the production of carnitine and keto-acid, especially leucine keto-acid, and in this regard RRF may also give a certain benefit for nutritional status [31].

Finally, RRF may affect nutritional status and protein intake through the continuous characteristic of residual renal solute elimination. The kidneys provide more continuous solute elimination compared with renal replacement therapies such as HD and CAPD. HD has the most intermittent characteristics. Because of this difference in continuity, a combination of dialysis and RRF will have a different effect on Kt/V urea than HD alone [32]. With regard to the relationship between dialysis Kt/V urea and nPCR, Bergstrom and Lindholm [5] showed that a continuous regimen of CAPD resulted in a greater increase in nPCR relating to the same increase in Kt/V urea than did intermittent HD, thus reinforcing the concept of the peak concentration hypothesis. In our results (Figure 3Go), patients with RRF had a steeper slope in the relationship between Kt/V urea and nPCR. Thus, the presence of RRF with continuous solute elimination may produce a more beneficial effect on dietary protein intake than in patients without RRF, despite total Kt/V urea being equal in both groups. These four factors may act solely or in combination and other unknown mechanisms may also be involved.

In conclusion, this study indicated that RRF in HD patients provides a beneficial effect on nutritional status. It is important to observe RRF over time and to maintain RRF by avoiding adverse events such as excessive dehydration, frequent hypotensive episodes and the use of nonsteroidal anti-inflammatory drugs or angiotensin-converting enzyme inhibitors, which possibly affect RRF. However, our observations can only be considered preliminary because of the relatively small number of patients and of the retrospective protocol. Thus, a prospective, large-scale study of RRF in dialysis patients will be required to investigate the validity of our results.



   References
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 9.12.98
Accepted in revised form: 21.10.99