The importance of residual renal function in dialysis patients - Core

review

http://www.kidney-international.org & 2006 International Society of Nephrology

The importance of residual renal function in dialysis patients AY-M Wang1 and K-N Lai1 1

University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China

Preserving residual renal function has always been the primary clinical goal for every nephrologist managing patients with chronic kidney disease. There is no reason why this important goal should not extend to patients with stage 5 chronic kidney disease receiving dialysis. Indeed, there is now clear evidence that preserving residual renal function remains important after the commencement of dialysis. Residual renal function contributes significantly to the overall health and well-being of dialysis patients. It not only provides small solute clearance but also plays an important role in maintaining fluid balance, phosphorus control, and removal of middle molecular uremic toxins, and shows strong inverse relationships with valvular calcification and cardiac hypertrophy in dialysis patients. Decline of residual renal function also contributes significantly to anemia, inflammation, and malnutrition in patients on dialysis. More importantly, the loss of residual renal function, especially in patients on peritoneal dialysis, is a powerful predictor of mortality. In addition, there is increasing evidence that residual renal and peritoneal dialysis clearance cannot be assumed to be equivalent qualitatively, thus indicating the need to preserve residual renal function in patients on dialysis. In this article, we will review evidence that residual renal function is important in dialysis patients (especially peritoneal dialysis) and outline potential strategies that may better preserve residual renal function in dialysis patients. Kidney International (2006) 69, 1726–1732. doi:10.1038/sj.ki.5000382; published online 12 April 2006 KEYWORDS: residual renal function; clearance; cardiovascular; malnutrition; preservation; dialysis

Correspondence: AYM Wang, University Department of Medicine, Queen Mary Hospital, University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China. E-mail: [email protected] Received 13 December 2005; revised 18 January 2006; accepted 24 January 2006; published online 12 April 2006 1726

IMPORTANCE OF RESIDUAL RENAL FUNCTION ON SURVIVAL OF DIALYSIS PATIENTS

The important association between residual renal function and survival in dialysis patients was first reported in the mid 1990s by Maiorca et al.1 They evaluated residual renal function as a separate factor and showed that the persistence of residual renal function conferred survival benefit in peritoneal dialysis patients.1 Several subsequent cohort studies observed similar findings that residual renal function but not the dose of peritoneal dialysis was a powerful predictor of survival in patients on peritoneal dialysis.2,3 This raised the need to review data from the original CANUSA study, which assumed an equivalence of renal and peritoneal dialysis clearance and showed that the total (sum of renal and peritoneal dialysis) small solute clearance predicts mortality in peritoneal dialysis patients.4 Indeed, reanalysis of data from the CANUSA study clearly demonstrated that the predictive power for mortality in patients on peritoneal dialysis was attributed to residual renal function and not to the dose of peritoneal dialysis.5 Although this should not lead to the assumption that the dose of peritoneal dialysis is unimportant, it does indicate that the contribution of residual renal and peritoneal dialysis clearance to the survival of peritoneal dialysis patients is not equivalent. On the other hand, studies in hemodialysis patients have also reported similar findings. An earlier network registry data from the United States as well as the more recent Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) study indicated the important contribution of residual renal function to the overall survival of hemodialysis patients.6,7 The recent ADEquacy of Peritoneal Dialysis in MEXico (ADEMEX) study lent further important evidence that residual renal and peritoneal dialysis clearance are not equivalent and thus not simply additive.8 In this prospective randomized controlled study, increasing peritoneal solute clearance showed no beneficial effect on survival in peritoneal dialysis patients as a whole or in the subgroup of anuric patients. Rather, residual renal function was predictive of outcome. This suggests that apart from providing small solute clearance, residual renal function has other important metabolic effects that may not be simply replaced by increasing the peritoneal small solute clearance and that may also explain the survival benefits it confers in dialysis patients. Although patients with and without residual renal Kidney International (2006) 69, 1726–1732

review

AY-M Wang and K-N Lai: Importance of residual renal function in dialysis patients

↓ Residual renal function

↑ Resting energy expenditure

↓ Removal of middle molecule uremic toxins, for example, p-cresol

Malnutrition

↓ Erythropoietin production and ↑ anemia

↑ Inflammation

Cardiac hypertrophy and heart failure

↓ Urea and creatinine clearance

Atherosclerosis and arteriosclerosis

↓ Sodium and fluid removal

↓ Phosphorus removal

Vascular and valvular calcification

↑ Overall and cardiovascular mortality ↓ Quality of life and well-being

Figure 1 | Importance of residual renal function in dialysis patients.

function are simply at different stages of progressive renal failure, our recent study showed that anuric peritoneal dialysis patients indeed had more adverse metabolic and cardiovascular profile as evidenced by more severe anemia with greater erythropoietin resistance, higher calcium phosphorus product, more inflammation and malnutrition, more hypertension, and greater cardiac hypertrophy, compared to patients with preserved residual renal function, and thus explained the greater overall and cardiovascular mortality observed in anuric patients.9 Figure 1 provides an overview of the importance of residual renal function in dialysis patients. RESIDUAL RENAL FUNCTION IN RELATION TO VOLUME CONTROL AND CARDIAC HYPERTROPHY

Residual renal function has been increasingly implicated to be important in maintaining fluid balance of dialysis patients, especially in patients on peritoneal dialysis. Greater extracellular fluid was observed in peritoneal dialysis patients with residual glomerular filtration rate below 2 ml/min than those with residual glomerular filtration rate above 2 ml/min.10 In the reanalysis of the CANUSA study, every 250 ml urine output was associated with a 36% reduction in overall mortality. In addition, the presence of urine output displaced renal small solute clearance from the multivariable Cox regression model.5 This gave indirect evidence that the degree of sodium and water removal by the diseased kidneys remains very important in determining the survival of peritoneal dialysis patients. Study by Ates et al.11 also confirmed the importance of total sodium and fluid removal in predicting survival of peritoneal dialysis patients. Indeed, peritoneal dialysis patients who had a history of volume Kidney International (2006) 69, 1726–1732

overload were noted to have more severe cardiac hypertrophy and dilatation as well as worse systolic and diastolic function.12 Given that cardiac hypertrophy is an important predictor of mortality in dialysis patients, our recent findings of more severe cardiac hypertrophy and dilatation as well as worse cardiac function among anuric peritoneal dialysis patients13 suggest that worsening volume control with loss of residual renal function may indeed be one of the important contributing factors for the adverse cardiovascular outcomes observed in anuric patients. As shown by Wang et al.13 and Menon et al.,14 blood pressure control worsened with time on peritoneal dialysis as residual renal function declines, and may be partly attributed to poor fluid control. In addition, loss of residual renal function was associated with more severe anemia owing to the loss of erythropoietin production, greater degree of hypoalbuminemia, and higher arterial pulse pressure,13 all of which were important risk factors for cardiac hypertrophy in dialysis patients. This suggested that the link between loss of residual renal function and cardiac hypertrophy in peritoneal dialysis patients may involve factors other than volume control. Residual renal function may also play a role in limiting cardiac hypertrophy by improving the overall removal of uremic toxins. This is evident by the increase in cardiac mass with decline in renal function in pre-dialysis chronic kidney disease patients,15 as well as the regression of cardiac hypertrophy and improvement of cardiac function in patients initiating continuous ambulatory peritoneal dialysis.16 The finding that residual renal function but not peritoneal dialysis small solute clearance showed a significant association with cardiac hypertrophy,13 together with regression of cardiac hypertrophy post-kidney transplant,17 suggests that some non-dialyzable 1727

review


uremic toxins may be important in mediating the progression of left ventricular hypertrophy in peritoneal dialysis patients and needs further evaluation. On the other hand, the importance of residual renal function in maintaining volume control and its relationship with cardiac hypertrophy are less well appreciated in hemodialysis patients, although the amount of extracellular water has also been described to be associated with hypertension and left ventricular hypertrophy in hemodialysis patients.18 IMPORTANT LINK BETWEEN RESIDUAL RENAL FUNCTION, PHOSPHORUS CONTROL, AND CALCIFICATION

Vascular/valvular calcification is an important complication in dialysis patients and is largely attributed to deranged mineral metabolism with a resulting abnormally increased calcium and phosphorus product. Cardiac valvular calcification predicts mortality and cardiovascular death in peritoneal dialysis patients.19 Vascular calcification is also associated with a greater mortality risk in hemodialysis patients.20 According to the study by Block et al.,21 a 6% increase in mortality risk was observed in hemodialysis patients for every 0.3 mmol/l increase in serum phosphate. Patients with serum phosphate of 2.1–2.5 mmol/l had an 18% higher mortality risk, whereas those with 2.6–5.5 mmol/l had a 39% higher risk of mortality than those with 1.5–1.8 mmol/l. Although continuous peritoneal dialysis is conventionally regarded to be better in controlling hyperphosphatemia than intermittent hemodialysis,22 our recent survey showed that hyperphosphatemia is also a frequent complication in peritoneal dialysis patients.23 Up to one-third of the peritoneal dialysis patients with preserved residual renal function and nearly half of the anuric patients were found to be hyperphosphatemia. Of more importance is the finding that the degree of residual glomerular filtration rate, despite average being below 2 ml/min per 1.73 m2, remained strongly associated with phosphorus control in peritoneal dialysis patients. Even though peritoneal dialysis clearance contributes significantly to the phosphorus control in peritoneal dialysis patients, our study clearly demonstrated the limitation of peritoneal dialysis alone in achieving adequate phosphorus control in anuric patients taking the Dialysis Outcome Quality Initiative (DOQI)-recommended dietary protein of at least 1 g/kg per day. The poor phosphorus control together with the greater inflammatory response in anuric peritoneal dialysis patients in turn translated to a greater calcification risk profile and thus predisposed to a higher incidence of valvular calcification, more arterial stiffening, and greater degree of cardiac hypertrophy, as shown in our recent unpublished observation. It is of interest to note that serum fetuin-A, a recently identified circulating inhibitor of calcification as well as a negative acute-phase reactant, showed no association with residual renal function,24 indicating that the increased risk of valvular calcification in anuric peritoneal dialysis patients is unlikely to be mediated via depletion of serum fetuin-A. On the other hand, there is so far no study that examined the 1728

importance of residual renal function in phosphorus control and calcification risk in hemodialysis patients. LINK BETWEEN RESIDUAL RENAL FUNCTION AND INFLAMMATION

Inflammation is highly prevalent in patients on dialysis, with a reported prevalence of around 12–65%.25 The degree of inflammation as denoted by C-reactive protein26,27 or other proinflammatory cytokines such as interleukin-628,29 is well established to be a powerful predictor of mortality and cardiovascular death in dialysis patients. Loss of residual renal function was associated with an increased inflammatory response as denoted by C-reactive protein30 or soluble vascular cell adhesion molecules31 in prevalent peritoneal dialysis patients. In incident peritoneal dialysis patients, lower residual renal function was also associated with increased inflammation.32 Likewise, study in pre-dialysis chronic kidney disease patients has reported a similar inverse relationship between renal function and pro-inflammatory mediators.33 Although the exact mechanism of association remains to be elucidated, the study has indicated that the relationship between residual renal function and inflammation is largely independent of the cardiovascular status of patients.34 Loss of residual renal function or uremia per se may enhance an inflammatory response via increased oxidative stress and this may lead to monocyte activation and cytokine production.35 The kidneys may play an important role in cytokine handling, as evidenced by the impaired cytokine clearance in nephrectomized rats.36 Conversely, the presence of inflammation also accelerated the decline of residual renal function.37 Nonetheless, irrespective of the underlying mechanisms of associations, our recent study showed that the loss of residual renal function together with inflammation and cardiac hypertrophy were closely interrelated phenomenon and they showed combined additive effects in enhancing the mortality and cardiovascular death risk of peritoneal dialysis patients.32 Using soluble vascular cell adhesion molecule as a marker of inflammation and endothelial activation, our recent study indicated that the association between loss of residual renal function and higher mortality and cardiovascular event risk was indeed mediated via its close associations with inflammation and endothelial activation.33 RESIDUAL RENAL FUNCTION AND NUTRITIONAL STATUS

Residual renal function is important in maintaining the nutritional status of dialysis patients. Study in peritoneal dialysis patients has clearly demonstrated the importance of residual renal function in determining the dietary protein and energy intake estimated using the food frequency questionnaire.38 Residual renal function contributes significantly to the overall nutritional status assessed using subjective global assessment,33 handgrip strength,39 or lean body mass40 in either hemodialysis or peritoneal dialysis patients. Micronutrients intake including those of water-soluble and fat-soluble vitamins and other minerals is also influenced by Kidney International (2006) 69, 1726–1732


the degree of residual renal function.41 It is of importance to note that in all these studies, peritoneal dialysis urea clearance, when considered as a separate factor, showed no independent relationship with nutritional status assessed using subjective global assessment, handgrip strength, or actual dietary intake by food frequency questionnaire in peritoneal dialysis patients. This provides important evidence that renal and peritoneal clearance have differential effects on nutritional status of peritoneal dialysis patients. Whether it is related to their differential effects on clearance of middlemolecular uremic toxins remains to be evaluated. On the other hand, there is recent evidence that loss of residual renal function also contributes significantly to malnutrition in peritoneal dialysis patients via its close association with increased resting energy expenditure.42 Resting energy expenditure accounts for 60–80% of the total energy expenditure. Its sustained increase may lead to energy imbalance and malnutrition if not compensated for by an increase in energy intake. In our recent study, increased resting energy expenditure was predictive of higher mortality and cardiovascular death in chronic peritoneal dialysis patients and was largely mediated via its close association with loss of residual renal function. Resting energy expenditure was not only increased in patients with underlying cardiovascular disease or more specifically in patients with the malnutrition–inflammation–atherosclerosis syndrome, but also showed a strong inverse relationship with loss of residual renal function in peritoneal dialysis patients. No association was however observed between resting energy expenditure and peritoneal dialysis clearance. In healthy subjects, the kidneys may account for up to 20% of the total resting energy expenditure. Although the effect of kidney failure on resting energy expenditure has remained controversial, our study provided evidence that despite loss of excretory functions, the diseased kidneys in end-stage renal disease patients retained important metabolic functions, as evidenced by the strong negative association between loss of residual renal function and resting energy expenditure in peritoneal dialysis patients. In addition, our study suggested that increased resting energy expenditure should be considered as a composite component of the malnutrition– inflammation–atherosclerosis syndrome that frequently accompanies patients with loss of residual renal function and contributes to malnutrition in anuric peritoneal dialysis patients. Further prospective study is needed to investigate whether a decline in residual renal function is indeed associated with an increase in resting energy expenditure. RESIDUAL RENAL FUNCTION AND REMOVAL OF MIDDLE MOLECULES AND OTHER UREMIC TOXINS

The other major aspect why renal and peritoneal dialysis clearance cannot be assumed to be equivalent lies in their differential capacity to remove middle molecules or other protein-bound uremic toxins. Residual renal function plays an important role in middle molecule clearance. Irrespective Kidney International (2006) 69, 1726–1732

review

of the modality of dialysis, patients with significant residual renal function showed lower b2-microglobulin than those with no residual renal function.43–45 A recent study by Bammens et al.46 provided evidence that although increasing peritoneal dialysis clearance may enhance clearance of watersoluble small solute clearance in patients with a decline in residual renal function, this was not the case for middle molecules and other protein-bound uremic toxins. Clearance of the protein-bound solute such as P-cresol has been shown to be largely determined by residual renal function in peritoneal dialysis patients, and its acumulation contributes to the uremic symptoms observed in peritoneal dialysis patients.47 RESIDUAL RENAL FUNCTION AND QUALITY OF LIFE

Given the diversified functions of residual renal function and its persistent important contribution to the overall health of dialysis patients, it is not surprising to find that residual renal function also contributes significantly to the quality of life of dialysis patients. As shown by the NECOSAD study,48 residual renal function and peritoneal dialysis clearance had very different impact on the quality of life of peritoneal dialysis patients. The presence of residual renal function had a positive influence on most dimensions of quality of life, especially physical functioning, vitality, kidney diseasespecific symptoms, effect of kidney disease on daily life and sleep disorders in peritoneal dialysis patients, whereas peritoneal dialysis clearance showed no effects on any of the quality of life dimensions. STRATEGIES FOR PRESERVING RESIDUAL RENAL FUNCTION

One potential strategy to preserve residual renal function may be to preferentially use peritoneal dialysis over hemodialysis in all incident patients with residual renal function. This concept is supported by a number of previous studies showing the superiority of peritoneal dialysis compared to hemodialysis in preserving residual renal function, although these studies were mostly observational and nonrandomized.49–52 The superiority of peritoneal dialysis remained even after selection bias (informative censoring) was ruled out.51 The exact mechanism of this finding is not clear, but may relate to greater hemodynamic stability with peritoneal dialysis and thus fewer ischemic insults to the kidney as well as greater nephrotoxic effects of inflammatory mediators from the extracorporeal circulation with hemodialysis. In fact, the better preservation of residual renal function in patients on peritoneal dialysis compared to hemodialysis has led to the adoption of an ‘integrative care approach’ where patients are started on peritoneal dialysis first, then transferred to hemodialysis when peritoneal dialysis-related problems arise. In one of the largest retrospective analyses, transfer of peritoneal dialysis patients to hemodialysis was indeed accompanied by an increase in survival compared to those remaining on peritoneal dialysis.53 A matched-pair analysis further indicated a survival advantage for patients adopting the integrative care 1729

review


approach compared to patients started on and remained on hemodialysis.53 On the other hand, patients using high-flux biocompatible membrane and ultrapure water for hemodialysis were noted to have a similar decline in residual renal function that was similar in rate to that in patients on continuous ambulatory peritoneal dialysis.54 This gave evidence that the greater decline of residual renal function in patients on hemodialysis may indeed be attributed to the use of bioincompatible membranes. Hemodialysis using modern synthetic membranes such as high-flux polysulfone membranes has been associated with a reduced rate of decline in residual renal function compared to those dialyzed using bioincompatible cellulosic membranes.55–57 Ultrapure dialysis fluid has also been shown to slow the loss of residual renal function in incident dialysis patients.55 Foreign material such as bioincompatible membrane in contact with the blood may activate peripheral blood mononuclear cells, resulting in activation of complement and inflammatory cascade and thus lead to further kidney injury.56 In other words, dialysis using biocompatible membrane and ultrapure water may be useful in reducing the loss of residual renal function in hemodialysis patients. Some earlier studies suggested a greater decline in residual renal function with automated peritoneal dialysis compared to continuous ambulatory peritoneal dialysis,57,58 and was hypothesized to be related to less stable fluid and osmotic load together with intermittent nature of automated peritoneal dialysis. Other study showed no association between the mode of peritoneal dialysis and loss of residual renal function.52 In a recent review by Van Biesen,59 it was pointed out that the association observed may be owing to some selection bias in patients receiving automated peritoneal dialysis. Another more recent study performed in incident peritoneal dialysis patients also observed greater loss of residual renal function with automated peritoneal dialysis compared to continuous ambulatory peritoneal dialysis.60 Further study is needed to clarify whether the mode of peritoneal dialysis influences the rate of decline of residual renal function. Avoiding the use of contrasts or nephrotoxic agents such as non-steroidal anti-inflammatory drugs or aminoglycoside appears a reasonable approach in protecting residual renal function. If contrast study is not avoidable, then preventive measures including adequate hydration, use of the smallest possible dose of contrast, use of iso-osmolal nonionic radiocontrast61 as well as prophylactic acetylcysteine62,63 should be considered. Although some earlier study suggested that aminoglycosides may increase loss of residual renal function,64 more recent study could not detect an association between aminoglycoside use and decline in residual renal function.65 Another recent randomized controlled study performed in peritoneal dialysis patients with peritonitis also indicated no greater loss of residual renal function in patients treated with aminoglycoside compared to those treated with ceftazidime within a 6-week duration,66 and may be explained by the intermittent, once daily dosing 1730

regimen of netilmicin, which has been shown to be less nephrotoxic.67 In terms of drug therapy, diuretics have been shown to increase sodium and water excretion and improve fluid balance in dialysis patients with residual renal function, but there is so far no evidence that it preserves residual renal function.68,69 Blockade of the renin–angiotensin system by angiotensin-converting enzyme inhibition or angiotensin receptor antagonism is a well-established approach for renoprotection in pre-dialysis chronic kidney disease patients. One recent open-label randomized controlled study showed that angiotensin-converting enzyme inhibitor, ramipril, may slow the rate of decline in residual renal function by close to 1 ml/min per 1.73 m2 per year in patients on continuous ambulatory peritoneal dialysis and reduce the progression to anuria.70 Similar results were also reported with the use of angiotensin receptor antagonist, valsartan, in patients on continuous ambulatory peritoneal dialysis.71 Although these two studies were both very small, they do add important supporting evidence that drugs with renoprotective effects in patients with stage 1–4 chronic kidney disease continue to exert renoprotection benefits and slow the progression to anuria in stage 5 chronic kidney disease patients on dialysis and thus should be continued in all dialysis patients with residual renal function. Maintaining good blood pressure control should also serve as an important measure in preserving residual renal function in dialysis patients, given the ample positive evidence in patients with chronic kidney disease. However, there is recent suggestion that strict volume control in peritoneal dialysis patients by severe salt restriction with progressive ultrafiltration till symptomatic may increase the risk of intravascular volume depletion and further compromise residual renal function.72 This indicates the importance to avoid overzealous ultrafiltration and intra-dialytic hypotension while trying to achieve fluid balance in dialysis patients, as this may have detrimental effects on residual renal function. CONCLUSIONS

There is convincing evidence that residual renal and peritoneal dialysis clearance cannot be assumed to be equivalent in peritoneal dialysis patients. Apart from providing small solute clearance, residual renal function continues to serve important metabolic and hemodynamic functions, and plays a crucial role in maintaining the overall cardiovascular health, nutritional status, and well-being of patients on dialysis, especially peritoneal dialysis, although the importance of residual renal function in hemodialysis patients is less well appreciated. Residual renal function has also been shown to have a significant impact on the survival of dialysis patients, especially in peritoneal dialysis, and its loss cannot simply be replaced by increasing the dose of peritoneal dialysis. It is time to realize that residual renal function is a very valuable asset to patients on dialysis and that the important goal to preserve residual renal function should continue even after patients are started on dialysis Kidney International (2006) 69, 1726–1732


treatment. More attention should be focused on preserving residual renal function in end-stage renal disease patients receiving long-term dialysis therapy.

21.

22.

ACKNOWLEDGMENTS

23.

The study was supported by funds from the Hong Kong Health Service Research Grant Number 6901023. 24.

REFERENCES 1. Maiorca R, Brunori G, Zubani R et al. Predictive value of dialysis adequacy and nutritional indices for mortality and morbidity in CAPD and HD patients. A longitudinal study. Nephrol Dial Transplant 1995; 10: 2295–2305. 2. az-Buxo JA, Lowrie EG, Lew NL et al. Associates of mortality among peritoneal dialysis patients with special reference to peritoneal transport rates and solute clearance. Am J Kidney Dis 1999; 33: 523–534. 3. Rocco M, Soucie JM, Pastan S, McClellan WM. Peritoneal dialysis adequacy and risk of death. Kidney Int 2000; 58: 446–457. 4. Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes. Canada–USA (CANUSA) Peritoneal Dialysis Study Group. J Am Soc Nephrol 1996; 7: 198–207. 5. Bargman JM, Thorpe KE, Churchill DN. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol 2001; 12: 2158–2162. 6. Shemin D, Bostom AG, Laliberty P, Dworkin LD. Residual renal function and mortality risk in hemodialysis patients. Am J Kidney Dis 2001; 38: 85–90. 7. Termorshuizen F, Dekker FW, van Manen JG et al. Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol 2004; 15: 1061–1070. 8. Paniagua R, Amato D, Vonesh E et al. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol 2002; 13: 1307–1320. 9. Wang AY, Woo J, Wang M et al. Important differentiation of factors that predict outcome in peritoneal dialysis patients with different degrees of residual renal function. Nephrol Dial Transplant 2005; 20: 396–403. 10. Konings CJ, Kooman JP, Schonck M et al. Fluid status in CAPD patients is related to peritoneal transport and residual renal function: evidence from a longitudinal study. Nephrol Dial Transplant 2003; 18: 797–803. 11. Ates K, Nergizoglu G, Keven K et al. Effect of fluid and sodium removal on mortality in peritoneal dialysis patients. Kidney Int 2001; 60: 767–776. 12. Wang AY, Sanderson J, Sea MM et al. Important factors other than dialysis adequacy associated with inadequate dietary protein and energy intakes in patients receiving maintenance peritoneal dialysis. Am J Clin Nutr 2003; 77: 834–841. 13. Wang AY, Wang M, Woo J et al. A novel association between residual renal function and left ventricular hypertrophy in peritoneal dialysis patients. Kidney Int 2002; 62: 639–647. 14. Menon MK, Naimark DM, Bargman JM et al. Long-term blood pressure control in a cohort of peritoneal dialysis patients and its association with residual renal function. Nephrol Dial Transplant 2001; 16: 2207–2213. 15. Levin A, Thompson CR, Ethier J et al. Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J Kidney Dis 1999; 34: 125–134. 16. Leenen FH, Smith DL, Khanna R, Oreopoulos DG. Changes in left ventricular hypertrophy and function in hypertensive patients started on continuous ambulatory peritoneal dialysis. Am Heart J 1985; 110: 102–106. 17. Rigatto C, Foley RN, Kent GM et al. Long-term changes in left ventricular hypertrophy after renal transplantation. Transplantation 2000; 70: 570–575. 18. Fagugli RM, Pasini P, Quintaliani G et al. Association between extracellular water, left ventricular mass and hypertension in haemodialysis patients. Nephrol Dial Transplant 2003; 18: 2332–2338. 19. Wang AY, Wang M, Woo J et al. Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study. J Am Soc Nephrol 2003; 14: 159–168. 20. Blacher J, Guerin AP, Pannier B et al. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001; 38: 938–942. Kidney International (2006) 69, 1726–1732

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42. 43.

review

Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998; 31: 607–617. Winchester JF, Rotellar C, Goggins M et al. Calcium and phosphate balance in dialysis patients. Kidney Int Suppl 1993; 41: S174–S178. Wang AY, Woo J, Sea MM et al. Hyperphosphatemia in Chinese peritoneal dialysis patients with and without residual kidney function: what are the implications? Am J Kidney Dis 2004; 43: 712–720. Wang AY, Woo J, Lam CW et al. Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 2005; 20: 1676–1685. Arici M, Walls J. End-stage renal disease, atherosclerosis, and cardiovascular mortality: is C-reactive protein the missing link? Kidney Int 2001; 59: 407–414. Wang AY, Woo J, Lam CW et al. Is a single time point C-reactive protein predictive of outcome in peritoneal dialysis patients? J Am Soc Nephrol 2003; 14: 1871–1879. Zimmermann J, Herrlinger S, Pruy A et al. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999; 55: 648–658. Panichi V, Maggiore U, Taccola D et al. Interleukin-6 is a stronger predictor of total and cardiovascular mortality than C-reactive protein in haemodialysis patients. Nephrol Dial Transplant 2004; 19: 1154–1160. Rao M, Guo D, Perianayagam MC et al. Plasma interleukin-6 predicts cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2005; 45: 324–333. Wang AY, Wang M, Woo J et al. Inflammation, residual kidney function, and cardiac hypertrophy are interrelated and combine adversely to enhance mortality and cardiovascular death risk of peritoneal dialysis patients. J Am Soc Nephrol 2004; 15: 2186–2194. Wang AY, Lam CW, Wang M et al. Circulating soluble vascular cell adhesion molecule 1: relationships with residual renal function, cardiac hypertrophy, and outcome of peritoneal dialysis patients. Am J Kidney Dis 2005; 45: 715–729. Chung SH, Heimburger O, Stenvinkel P et al. Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis. Nephrol Dial Transplant 2001; 16: 2240–2245. Pecoits-Filho R, Heimburger O, Barany P et al. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis 2003; 41: 1212–1218. Shlipak MG, Fried LF, Crump C et al. Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation 2003; 107: 87–92. Witko-Sarsat V, Friedlander M, Nguyen KT et al. Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol 1998; 161: 2524–2532. Bemelmans MH, Gouma DJ, Buurman WA. Influence of nephrectomy on tumor necrosis factor clearance in a murine model. J Immunol 1993; 150: 2007–2017. Shin SK, Noh H, Kang SW et al. Risk factors influencing the decline of residual renal function in continuous ambulatory peritoneal dialysis patients. Perit Dial Int 1999; 19: 138–142. Wang AY, Sea MM, Ip R et al. Independent effects of residual renal function and dialysis adequacy on actual dietary protein, calorie, and other nutrient intake in patients on continuous ambulatory peritoneal dialysis. J Am Soc Nephrol 2001; 12: 2450–2457. Wang AY, Sea MM, Ho ZS et al. Evaluation of handgrip strength as a nutritional marker and prognostic indicator in peritoneal dialysis patients. Am J Clin Nutr 2005; 81: 79–86. Suda T, Hiroshige K, Ohta T et al. The contribution of residual renal function to overall nutritional status in chronic haemodialysis patients. Nephrol Dial Transplant 2000; 15: 396–401. Wang AY, Sea MM, Ip R et al. Independent effects of residual renal function and dialysis adequacy on dietary micronutrient intakes in patients receiving continuous ambulatory peritoneal dialysis. Am J Clin Nutr 2002; 76: 569–576. Wang AY, Sea MM, Tang N et al. Resting energy expenditure and subsequent mortality risk in peritoneal dialysis patients. J Am Soc Nephrol 2004; 15: 3134–3143. Maeda K, Shinzato T, Ota T et al. Beta-2-microglobulin generation rate and clearance rate in maintenance hemodialysis patients. Nephron 1990; 56: 118–125.

1731

review

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56.

57.


Amici G, Virga G, Da RG et al. Serum beta-2-microglobulin level and residual renal function in peritoneal dialysis. Nephron 1993; 65: 469–471. Brown PH, Kalra PA, Turney JH, Cooper EH. Serum low-molecular-weight proteins in haemodialysis patients: effect of residual renal function. Nephrol Dial Transplant 1988; 3: 169–173. Bammens B, Evenepoel P, Verbeke K, Vanrenterghem Y. Time profiles of peritoneal and renal clearances of different uremic solutes in incident peritoneal dialysis patients. Am J Kidney Dis 2005; 46: 512–519. Bammens B, Evenepoel P, Verbeke K, Vanrenterghem Y. Removal of middle molecules and protein-bound solutes by peritoneal dialysis and relation with uremic symptoms. Kidney Int 2003; 64: 2238–2243. Termorshuizen F, Korevaar JC, Dekker FW et al. The relative importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. Am J Kidney Dis 2003; 41: 1293–1302. Rottembourg J, Issad B, Gallego JL et al. Evolution of residual renal function in patients undergoing maintenance haemodialysis or continuous ambulatory peritoneal dialysis. Proc Eur Dial Transplant Assoc 1983; 19: 397–403. Misra M, Vonesh E, Van Stone JC et al. Effect of cause and time of dropout on the residual GFR: a comparative analysis of the decline of GFR on dialysis. Kidney Int 2001; 59: 754–763. Lysaght MJ, Vonesh EF, Gotch F et al. The influence of dialysis treatment modality on the decline of remaining renal function. ASAIO Trans 1991; 37: 598–604. Moist LM, Port FK, Orzol SM et al. Predictors of loss of residual renal function among new dialysis patients. J Am Soc Nephrol 2000; 11: 556–564. Van BW, Vanholder RC, Veys N et al. An evaluation of an integrative care approach for end-stage renal disease patients. J Am Soc Nephrol 2000; 11: 116–125. McKane W, Chandna SM, Tattersall JE et al. Identical decline of residual renal function in high-flux biocompatible hemodialysis and CAPD. Kidney Int 2002; 61: 256–265. Schiffl H, Lang SM, Fischer R. Ultrapure dialysis fluid slows loss of residual renal function in new dialysis patients. Nephrol Dial Transplant 2002; 17: 1814–1818. Stannat S, Bahlmann J, Kiessling D et al. Complement activation during hemodialysis. Comparison of polysulfone and cuprophan membranes. Contrib Nephrol 1985; 46: 102–108. Holley JL, Aslam N, Bernardini J et al. The influence of demographic factors and modality on loss of residual renal function in incident peritoneal dialysis patients. Perit Dial Int 2001; 21: 302–305.

1732

58.

59.

60.

61. 62.

63. 64.

65.

66.

67.

68.

69.

70.

71.

72.

Hufnagel G, Michel C, Queffeulou G et al. The influence of automated peritoneal dialysis on the decrease in residual renal function. Nephrol Dial Transplant 1999; 14: 1224–1228. Van BW, Veys N, Vanholder R, Lameire N. The role of APD in the improvement of outcomes in an ESRD program. Semin Dial 2002; 15: 422–426. Rodriguez-Carmona A, Perez-Fontan M, Garca-Naveiro R et al. Compared time profiles of ultrafiltration, sodium removal, and renal function in incident CAPD and automated peritoneal dialysis patients. Am J Kidney Dis 2004; 44: 132–145. Aspelin P, Aubry P, Fransson SG et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003; 348: 491–499. Tepel M, van der GM, Schwarzfeld C et al. Prevention of radiographiccontrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343: 180–184. Birck R, Krzossok S, Markowetz F et al. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003; 362: 598–603. Shemin D, Maaz D, St PD et al. Effect of aminoglycoside use on residual renal function in peritoneal dialysis patients. Am J Kidney Dis 1999; 34: 14–20. Baker RJ, Senior H, Clemenger M, Brown EA. Empirical aminoglycosides for peritonitis do not affect residual renal function. Am J Kidney Dis 2003; 41: 670–675. Lui SL, Cheng SW, Ng F et al. Cefazolin plus netilmicin versus cefazolin plus ceftazidime for treating CAPD peritonitis: effect on residual renal function. Kidney Int 2005; 68: 2375–2380. Barclay ML, Kirkpatrick CM, Begg EJ. Once daily aminoglycoside therapy. Is it less toxic than multiple daily doses and how should it be monitored? Clin Pharmacokinet 1999; 36: 89–98. Medcalf JF, Harris KP, Walls J. Role of diuretics in the preservation of residual renal function in patients on continuous ambulatory peritoneal dialysis. Kidney Int 2001; 59: 1128–1133. van Olden RW, Guchelaar HJ, Struijk DG et al. Acute effects of high-dose furosemide on residual renal function in CAPD patients. Perit Dial Int 2003; 23: 339–347. Li PK, Chow KM, Wong TY et al. Effects of an angiotensin-converting enzyme inhibitor on residual renal function in patients receiving peritoneal dialysis. A randomized, controlled study. Ann Intern Med 2003; 139: 105–112. Suzuki H, Kanno Y, Sugahara S et al. Effects of an angiotensin II receptor blocker, valsartan, on residual renal function in patients on CAPD. Am J Kidney Dis 2004; 43: 1056–1064. Gunal AI, Duman S, Ozkahya M et al. Strict volume control normalizes hypertension in peritoneal dialysis patients. Am J Kidney Dis 2001; 37: 588–593.

Kidney International (2006) 69, 1726–1732