Role Of Residual Renal Function Research Articles

Predictors of hyporesponsiveness to ESAs in peritoneal dialysis patients: the role of residual renal function

Predictors of hyporesponsiveness to ESAs in peritoneal dialysis patients: the role of residual renal function

The role of residual renal function on potassium intake and excretion in patients on peritoneal dialysis.

Patients on chronic dialysis are at increased risk of developing disorders in potassium balance. The preservation of residual renal function (RRF), frequently observed in patients on peritoneal dialysis (PD), may contribute to better control of serum potassium. This study aimed to investigate the role residual renal function on potassium intake and excretion in PD patients. In this cross-sectional study, dietary potassium was evaluated by the 3-day food record. Potassium concentration was determined in serum, 24h dialysate, stool ample, and 24h urine of patients with diuresis > 200mL/day, who were considered non-anuric. Fifty-two patients, 50% men, 52.6 ± 14.0years, and PD vintage 19.5 [7.0-44.2] months, were enrolled. Compared to the anuric group (n = 17, 33%), the non-anuric group (n = 35, 67%) had lower dialysate potassium excretion (24.8 ± 5.3 vs 30.9 ± 5.9mEq/d; p = 0.001), higher total potassium intake (44.5 ± 16.7 vs 35.1 ± 8.1mEq/d; p = 0.009) and potassium intake from fruit (6.2 [2.4-14.7] vs 2.9 [0.0-6.0]mEq/d; p = 0.018), and no difference in serum potassium (4.8 ± 0.6 vs 4.8 ± 0.9mEq/L; p = 0.799) and fecal potassium (2.2 ± 0.5 vs 2.1 ± 0.7mEq/L; p = 0.712). In non-anuric patients, potassium intake correlated directly with urinary potassium (r = 0.40; p = 0.017), but not with serum, dialysate, or fecal potassium. In the anuric group, potassium intake tended to correlate positively with serum potassium (r = 0.48; p = 0.051) and there was no correlation with dialysate or fecal potassium. The presence of residual renal function constitutes an important factor in the excretion of potassium, which may allow the adoption of a less-restrictive diet.

Residual renal function in incremental haemodialysis.

ABSTRACTBackgroundEquivalent renal clearance (EKR) and standard clearance (stdK) are continuous-equivalent measures of urea clearance and include residual renal function (RRF), if calculated appropriately. RRF is qualitatively better than dialysis with equivalent urea clearance. Instructions for calculating stdKt/V (stdK scaled by urea distribution volume) and its target value (2.3) are presented in the Kidney Disease Outcomes Quality Initiative (KDOQI) 2015 guidelines. EKR targets have not been defined in the current guidelines.MethodsThe stdKt/V in the presence of RRF was calculated with the classic double-pool urea kinetic model and with the Daugirdas modification, which accentuates the renal contribution. The EKR/V (EKR scaled by urea distribution volume) was calculated with nominal and adjusted renal clearance (renal urea clearance multiplied by a weighting factor). New prescriptions with different continuous clearance targets were generated by a computer program.ResultsThe contribution of RRF can be weighted flexibly in EKR/V by adjusting the renal clearance value. A new therapeutic index, EKR/Va (adjusted total EKR/V), was introduced. In 62 incremental dialysis sessions of 16 patients with a renal urea clearance (Kr) of over 1 mL/min, the Daugirdas stdKt/V was, on average, 7.5% higher than classic stdK/V and adjusted EKR/V was 14.4% higher than unadjusted EKR/V.ConclusionsThe stdKt/V is not an optimal descriptor of haemodialysis urea clearance. With EKR/V, the role of RRF can be evaluated more sensibly. Using adjusted EKR/V as the target permits less frequent incremental dialysis.

Even a Moderate Fluid Removal Rate during Individualised Haemodialysis Session Times Is Associated with Decreased Patient Survival

Background: Several studies report that fluid removal rate (FRR) above 10-13 mL/h/kg is associated with increased mortality in haemodialysis (HD) patients. Aim: The aims of this study are to assess the influence of moderate FRR on survival in a cohort of prevalent dialysis patients with various dialysis session times and to challenge the FRR thresholds associated with increased mortality risk reported previously. Methods: Interdialytic weight gain (IDWG) and FRR (calculated from ultrafiltration [UF], target weight, and session time prescriptions) were studied in 190 prevalent dialysis patients (female: 42%, mean age: 69.5 years, median vintage: 40.2 months, diabetes: 34.7%, loop diuretic prescription: 5.8%) and averaged during the final quarter of 2010. Patient survival was analysed using Kaplan-Meier and Cox-multivariate analyses. Results: The median IDWG, median session time, and median FRR were 2.33 kg (-0.54-4.57), 5.0 h (3.9-8.0 h), 6.8 mL/h/kg (1.3-16.7), respectively, and FRR was ≥10 mL/h/kg in 11.6% of the patients. The Kaplan-Meier analysis showed decreased patient survival when the FRR was above the median (6.8 mL/h/kg; p = 0.012). The FRR was found to be independently associated with increased mortality (hazard ratio 1.15 [95% CI 1.02-1.29]; p = 0.027) using stepwise Cox proportional hazard regression analysis, including age, vintage, gender, body mass index (BMI), serum albumin level, β2-microglobulin level, cardiovascular and diabetes history, and session time. Online haemodiafiltration did not change this result. The role of residual renal function was unlikely because 74% of the patients had a vintage of >18 months, a minority (5.8%) were prescribed loop diuretics (a surrogate of significant urine output) and β2-microglobulin level was not different in patients who were below or above the FRR median. Conclusion: We concluded that the FRR threshold above which there is an increased mortality is lower than what has been reported (7.8 mL/h/kg). It raises the question of the hazard of fluid removal and intermittence of standard HD.

The Role of Residual Renal Function in Diabetic Peritoneal Dialysis Patients

Peritoneal dialysis (PD) is a treatment method used in home renal replacement therapy. Recently, there has been greater focus on residual renal function (RRF) in PD patients. RRF in PD patients is clinically significant, as it contributes to survival of the treatment, as well as patient mortality rates. Not only does decreased RRF cause poor management of water removal, but also increases risk of mortality as well as PD withdrawal due to over hydration. Diabetic patients are at higher risk of mortality/comorbidities and loss of RRF than patients with other diseases. Loss of RRF is the main cause of over hydration, poor quality of life (QOL), withdrawal of PD, and high mortality rate in dialysis patients; therefore, it is clinically important to maintain RRF. Control of blood pressure, inhibition of the renin-angiotensin system, decreased proteinuria, dietary intervention, avoidance of nephrotoxins, and glucose control should be considered for maintaining RRF in dialysis patients. Additionally, sarcopenia and frailty are issues of significant importance, especially in patients with end-stage renal disease (ESRD). As metabolic acidosis can be a complication of ESRD, anemia, uremia, and appetite loss are side effects; loss of appetite and inflammation are also associated with mortality. To ensure good QOL, PD survival, and low mortality risk, it is imperative to maintain RRF. Aside from the use of icodextrin or large amounts of diuretics, tolvaptan—often used at initiation of PD in patients with over hydration-may also be beneficial in maintaining RRF. RRF that is positively maintained aids in enhancing the appetite and improving malnutrition and inflammation, both of which contribute to loss of RRF. Moreover, enhanced appetite may improve QOL and prevent the possibility of sarcopenia and frailty in PD patients. In hemodialysis patients, tolvaptan also may be useful in the preservation of RRF and decreased mortality rate, as well as improved QOL.

Heart Rate Variability in Peritoneal Dialysis Patients: What Is the Role of Residual Renal Function?

Background: The relationship between heart rate variability (HRV) and residual renal function (RRF) has not been elucidated previously. Methods: In this cross-sectional study, HRV was evaluated in 71 peritoneal dialysis patients. Patients were divided into RRF decline group, RRF stable group and anuric group. Results: RRF was negatively correlated with SDNN (r = –0.284, p = 0.017), TP (r = –0.247, p = 0.039), and HF (r = –0.238, p = 0.047). Significant sympathetic nerve activation was found in the RRF decline group (significantly lower SDNN, SDSD, RMSSD, pNN50, LF, HF, TP and higher LF/HF ratio) as compared to the RRF stable and anuric groups. Besides, significantly parasympathetic activation was found in the anuric group (the lowest LF/HF ratio as compared to the other groups (both p < 0.05). Multivariate stepwise regression analysis showed that the status of RRF was an independent factor associated with HRV parameters. Conclusion: This study showed autonomic nervous function in peritoneal dialysis patients was associated with a different status of RRF.

High Correlation Between Clearance of Renal Protein‐Bound Uremic Toxins (Indoxyl Sulfate and p‐Cresyl Sulfate) and Renal Water‐Soluble Toxins in Peritoneal Dialysis Patients

Peritoneal dialysis (PD) is characterized by a slow continuous removal of solutes. Traditionally, dialysis adequacy is quantified by referring to the kinetics of urea nitrogen (UN) and creatinine (Cr) clearance. The efficacy of middle molecular substances and protein-bound solutes as markers for peritoneal dialysis adequacy is not clear. The aim of this cross-sectional study was to investigate correlations between the clearance of indoxyl sulfate (IS), p-cresyl sulfate (PCS), UN, and Cr in the peritoneum and kidneys and to compare the overall clearances of IS and PCS between non-anuric and anuric groups in PD patients. We recruited a total of 175 patients who had been undergoing continuous ambulatory PD (CAPD) or automated PD (APD) for at least 4 months. We measured total IS and PCS concentrations in serum, dialysate, and urine samples. Free IS and PCS concentrations were measured in all serum samples. IS and PCS clearances via both kidney and peritoneum were measured. The mean concentration of IS in the urine samples was 9.2-fold higher than that in the dialysate samples, and concentration of PCS in the urine samples was 8.5-fold higher than that in the dialysate samples. Peritoneal UN and Cr clearances were not correlated with peritoneal PCS clearance (P > 0.05) but were mildly correlated with peritoneal IS clearance. The peritoneal IS and PCS clearances in the different peritoneal equilibration test groups were similar. The renal UN and Cr clearances were strongly correlated with renal PCS and IS clearances (P > 0.89, P < 0.001). In addition, non-anuric patients showed better elimination of total PCS (10.3 mg/day [range, 1.6-19.8] vs. 5.2 mg/day [range, 0-14]; P < 0.001] and IS (37.9 mg/day [range, 25.6-56.7] vs. 24.8 mg/day [range, 17.1-41.6]; P < 0.001) than anuric patients. This cross-sectional study showed that peritoneal clearance of water-soluble solutes is not correlated with that of PCS but is mildly correlated with that of IS. However, the renal clearances of IS and PCS show strong positive correlation with the renal clearances of UN and Cr. This study confirms the important role of residual renal function in the removal of protein-bound uremic toxins.

Reduced Residual Renal Function is Associated with Endothelial Dysfunction in Patients Receiving Peritoneal Dialysis

Endothelial dysfunction, which contributes to atherosclerosis and arteriosclerosis, commonly accompanies end-stage renal disease (ESRD). However, little is known about the role of residual renal function (RRF) in endothelial protection in ESRD patients. This study aimed to investigate the relationship between endothelial function and RRF in patients undergoing peritoneal dialysis (PD). This was a cross-sectional study involving 72 prevalent PD patients. Demographic and clinical data were recorded and residual glomerular filtration rate (GFR), Kt/V urea, and serum concentrations of inflammatory markers were measured. Endothelial function was assessed by brachial artery endothelium-dependent vasodilation [flow-mediated dilation (FMD)] to reactive hyperemia following 5 minutes of forearm ischemia. In patients with FMD% above the median value (FMD > 2.41%), residual GFR was significantly higher compared to that in patients with FMD% below the median [1.50 (0 - 9.64) vs 0.48 (0 - 3.89) mL/min/1.73 m(2), P = 0.026]. Correlation analyses revealed that residual GFR (ρ = 0.381, P = 0.001) and total Kt/V urea (γ = 0.408, P < 0.001) were positively correlated with FMD%, whereas PD duration (γ = -0.351, P = 0.003), high-sensitivity C-reactive protein (ρ = -0.345, P = 0.003), pulse pressure (γ = -0.341, P = 0.003), and age (γ = -0.403, P < 0.001) were inversely correlated with FMD%. In contrast, there was no correlation between peritoneal Kt/V urea and FMD%. In multivariate linear regression analysis adjusted for these factors, residual GFR was found to be an independent determinant of FMD% (β = 0.317, P = 0.017). This study shows that RRF is independently associated with endothelial dysfunction in ESRD patients on PD, suggesting that RRF may contribute to endothelial protection in these patients.

Residual renal function is an independent determinant of serum FGF-23 levels in dialysis patients

Both poor residual renal function (RRF) and high fibroblast growth factor 23 (FGF-23) levels are associated with arterial stiffness, left ventricular hypertrophy and increased (cardiovascular) mortality. Whether FGF-23 and RRF are interrelated is unknown. We performed a prospective observational cohort study in 35 peritoneal dialysis (PD) patients with evaluation at 1, 6, 12 and 24 months after start of PD. In addition, the role of RRF was assessed in a cross-sectional observational cohort study including 68 prevalent haemodialysis patients. RRF significantly declined over time in PD patients. This decline was parallelled by a significant increase of both serum phosphorus and FGF-23 levels. In the prevalent dialysis cohort, RRF was found to be inversely associated with serum FGF-23 levels, independent of dialysis vintage, dialytic creatinine clearance, estimates of dietary phosphate intake (i.e. normalized protein nitrogen appearance), active vitamin D therapy and serum phosphorus and calcium levels. RRF, serum phosphorus and calcium levels and active vitamin D therapy explain 69% of the variation in FGF-23. The 38 anuric patients had higher FGF-23 levels but similar serum phosphorus levels. We demonstrate an important association between RRF and FGF-23, independent of classical determinants. This favours the hypothesis that the ailing kidney directly contributes to the raised FGF-23 levels. Whether FGF-23 is associated with poor outcomes independent of RRF, or vice versa, remains to be clarified.

Role of Residual Renal Function in Phosphate Control and Anemia Management in Chronic Hemodialysis Patients

There is increasing awareness that residual renal function (RRF) has beneficial effects in hemodialysis (HD) patients. The aim of this study was to investigate the role of RRF, expressed as GFR, in phosphate and anemia management in chronic HD patients. Baseline data of 552 consecutive patients from the Convective Transport Study (CONTRAST) were analyzed. Patients with a urinary output≥100 ml/24 h (n=295) were categorized in tertiles on the basis of degree of GFR and compared with anuric patients (i.e., urinary output<100 ml/24 h, n=274). Relations between GFR and serum phosphate and erythropoiesis-stimulating agent (ESA) index (weekly ESA dose per kg body weight divided by hematocrit) were analyzed with multivariable regression models. Phosphate levels were between 3.5 and 5.5 mg/dl in 68% of patients in the upper tertile (GFR>4.13 ml/min per 1.73 m2), as compared with 46% in anuric patients despite lower prescription of phosphate-binding agents. Mean hemoglobin levels were 11.9±1.2 g/dl with no differences between the GFR categories. The ESA index was 31% lower in patients in the upper tertile as compared with anuric patients. After adjustments for patient characteristics, patients in the upper tertile had significantly lower serum phosphate levels and ESA index as compared with anuric patients. This study suggests a strong relation between RRF and improved phosphate and anemia control in HD patients. Efforts to preserve RRF in HD patients could improve outcomes and should be encouraged.

Reduced residual renal function is a risk of peritonitis in continuous ambulatory peritoneal dialysis patients

Loss of residual renal function (RRF) contributes to anaemia, inflammation and malnutrition and is also a strong predictor of mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. However, the role of RRF on peritonitis is not yet clearly established. This study aimed to evaluate the effect of RRF on the development of peritonitis. Study subjects were 204 end-stage renal disease (ESRD) patients who started PD from January 2000 to December 2005. Biochemical and clinical data within 1 month of PD commencement were considered as baseline. To determine risk factors for peritonitis, multivariate Cox regression was performed. Kaplan-Meier analysis and log-rank test were used to examine the difference of peritonitis-free period according to the presence of diabetes and RRF. On univariate analysis based on baseline data in first peritonitis, diabetes was less prevalent and RRF (6.7+/-2.6 vs 4.0+/-2.3 ml/min/1.73 m2, P<0.01), haemoglobin (10.9+/-1.2 vs 10.6+/-1.2 g/dl, P<0.05) and serum albumin level (3.6+/-0.4 vs 3.4+/-0.4 g/dl, P<0.01) were significantly higher in the peritonitis-free group. Kaplan-Meier analysis showed that time to first PD peritonitis episode was significantly longer in the non-diabetic patients (P<0.001) and in patients with higher residual GFR (P<0.001). Multivariate analysis showed that diabetes [hazard ratio(HR) 1.64, P<0.05] and RRF (per 1 ml/min/1.73 m2 increase, HR 0.81, P<0.01) were independent risk factors. Our study revealed that RRF and diabetes were risk factors for peritonitis. These results suggest that preservation of RRF should be viewed as a protective strategy to reduce peritonitis.

Is it time to revisit residual renal function in haemodialysis? (Review Article)

Residual renal function (RRF) is not currently emphasized for patients undergoing haemodialysis (HD). The role of RRF is well recognized in the peritoneal dialysis population as studies have clearly demonstrated a survival benefit with preservation of RRF. There is however, data to suggest that RRF is important in HD patients as well. Contemporary HD therapies using high flux biocompatible synthetic dialysers, bicarbonate buffered ultrapure dialysis fluids with ultrafiltration control appear to allow better preservation of RRF. The long held belief that peritoneal dialysis is better at preserving RRF than HD may no longer be true. More robust studies are required to determine the relative importance of RRF in HD and strategies to best preserve this vital asset.

Adequacy of peritoneal dialysis and the importance of preserving residual renal function

The well-being and survival of dialysis patients not only depend on the removal of waste products and excess fluid, but also on the prevention of cardiovascular complications by maintaining normovolaemia and adequate blood pressure and avoidance of ectopic calcification. Also, the maintenance of nutritional status and adequate removal of middle molecules are amongst the most important issues in long-term renal replacement therapy. In this review, attention is given to optimal peritoneal small solute clearance and Kt/V and to the evidence concerning the role of residual renal function. In addition, factors that can influence this residual function are also discussed.

Metabolic Acidosis in Peritoneal Dialysis Patients: The Role of Residual Renal Function

Background: Metabolic acidosis (MA) is common in chronic renal insufficiency (CRI) patients, and its pattern changes as renal function deteriorates. Although the prevalence of acidosis in peritoneal dialysis has been reported to be rather high, the causes of it have not been well studied. The present study was performed to examine the prevalence of metabolic acidosis in our continuous ambulatory peritoneal dialysis (CAPD) patients and its possible causes. Methods: In this cross-sectional study, we analyzed data from patients who received maintenance CAPD in our hospital and had been on dialysis for at least one month. Patients’ demographic features, medications, and intercurrent medical conditions were recorded. Data including blood biochemistry, dialysis adequacy, and nutrition were collected. A serum bicarbonate concentration of less than 23 mmol/l was defined as having acidosis. The normal value of the serum anion gap (AG) was defined as 12 ± 4 mmol/l. Results: A total of 154 patients (76 males and 78 females) with age of 60.04 ± 13.92 years and the time on dialysis of 16.83 ± 21.59 months were included in this study. Sixty-six patients (43%) had a serum bicarbonate of less than 23 mmol/l, among whom 12 patients (8%) were identified as having MA with increased AG, 54 (35%) were identified as having MA with normal AG. Patients who had better residual renal function (RRF) had a significantly lower serum bicarbonate level despite their higher total KT/V_urea as compared to those with lower RRF. In addition, patients with MA and normal AG had the highest RRF and highest total KT/V_urea. All patients with MA and increased AG had significantly lower values of dietary protein intake (DPI) as compared to their values of normalized protein nitrogen appearance (nPNA), and had higher serum urea and phosphate levels as compared with those patients without MA. Conclusion: Our study suggested that CAPD patients with better RRF were more susceptible to metabolic acidosis, which was characterized by normal anion gap and hyperchloremia. Thus, we speculate that renal loss of bicarbonate may to a large extent be responsible for the occurrence of MA in these patients.

Residual renal function and post dialysis urea rebound.

Kt/v is used to estimate haemodialysis prescription and treatment adequacy and usually does not include evaluation of urea rebound. In addition urea clearance provided by the presence of residual renal function (RRF) is additive to dialytic urea clearance. Rebound is a phenomenon involving other molecules such as creatinine and phosphorus. The aim of this study was to investigate the role of RRF on post dialysis urea, creatinine and phosphorus rebounds. We investigated 7 patients with RRF (group 1) and 7 uraemic anuric patients (group 2). Urea rebound was lower in group 1 than group 2: 9.5 +/- 4% vs 18 +/- 7% (p = 0.04). Creatinine rebound and phosphorus rebound were similar in both groups 15.2 +/- 9% group 1 vs 14.6 +/- 5% group 2 (p = NS) and 16.7 +/- 7% group 1 vs 20 +/- 7% group 2 (p = NS) respectively. Our data suggest Kt/v calculated without considering rebound overestimates haemodialysis efficacy.

Separating the Effects of Hemodialysis Dose and Nutrition: In Search of the Optimal Dialysis Dose

The renal community owes Dr. Frank Gotch a great debt for the contributions that he has made to clarify the relationship between urea clearance and the dose of dialysis. With John Sargent he developed the mathematical approach to hemodialysis (1). In his seminal publication he re-analyzed data of the National Cooperative Dialysis Study to establish the association between the theoretically derived Kt/V for urea and clinical outcomes (2). Although diffusion equations are well understood and are used in many fields of science, Dr. Gotch’s persistent and tireless efforts to identify and quantitate the specific aspects of this process in dialysis through formal kinetic modeling, yielding additionally the protein catabolic rate (PCR) (3), have been extremely valuable to both patients and clinicians alike. The continuing measurement of Kt/ Vurea in every dialysis unit is a lasting tribute to Dr. Gotch’s contributions. Accurate measurement of the dose of dialysis is important in part because of its relationship to patient outcomes and to the cost of dialysis. Further, the concepts underlying the dose of episodic hemodialysis, pioneered by Dr. Gotch, are of practical importance in understanding the role of residual renal function and in quantitateing the dose of continuous dialytic procedures. Kt/V has been found to be one of the key modifiable components of the practice of hemodialysis.