Rate of Decline of Kidney Function, Modality Choice, and Survival in Elderly Patients with Advanced Kidney Disease.

AIM: In elderly, dependent patients with advanced chronic kidney disease, dialysis may confer only a small survival advantage over conservative kidney management (CKM). We investigated the role of rate of decline of kidney function on treatment choices and survival. METHODS: We identified a retrospective (1995-2010) cohort of patients aged over 75 years, with progressive kidney impairment and an estimated glomerular filtration rate (eGFR) between 10 and 15 ml/min/1.73 m2. All subsequently chose to be treated by either dialysis or CKM. Patients were followed for a minimum of 3 years. RESULTS: Of 250 patients identified, 92 (37%) opted for dialysis and 158 (63%) for CKM. Mean age was 80.9 ± 4.0 years. eGFR was 13.3 ± 1.4 initially and 8.7 ± 3.0 ml/min/1.73 m2 at follow-up. Both were similar in those on dialysis and CKM pathways. Rate of decline of eGFR was more rapid in those choosing dialysis (0.45 (interquartile range, IQR 0.64) vs. 0.21 (IQR 0.28) ml/min/1.73 m2/month, p < 0.001), and independently predicted choice of CKM. In patients with high comorbidity, choice of dialysis was associated with a non-significant adjusted survival advantage of 5 months. Inclusion in models of time dependent eGFR during follow-up (eGFRtd) - a reflection of the rate of decline of kidney function - showed it to be independently associated with mortality risk in those on the CKM (p < 0.001) but not on the dialysis pathway. CKM pathway patients at the 25th centile of eGFRtd had an adjusted survival of 7 months compared to 63 months for those at the 75th centile. CONCLUSIONS: Rate of decline of kidney function is a determinant of CKM choice in elderly patients and is associated with mortality risk in patients of the CKM pathway. These findings should inform counselling.

Quality of life and survival in patients with advanced kidney failure managed conservatively or by dialysis.

BACKGROUND AND OBJECTIVES: Benefits of dialysis in elderly dependent patients are not clearcut. Some patients forego dialysis, opting for conservative kidney management (CKM). This study prospectively compared quality of life and survival in CKM patients and those opting for dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Quality-of-life assessments (Short-Form 36, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale) were performed every 3 months for up to 3 years in patients with advanced, progressive CKD (late stage 4 and stage 5). RESULTS: After 3 years, 80 and 44 of 170 patients had started or were planned for hemodialysis (HD) or peritoneal dialysis, respectively; 30 were undergoing CKM; and 16 remained undecided. Mean baseline estimated GFR ± SD was similar (14.0 ± 4.0 ml/min per 1.73 m(2)) in all groups but was slightly higher in undecided patients. CKM patients were older, more dependent, and more highly comorbid; had poorer physical health; and had higher anxiety levels than the dialysis patients. Mental health, depression, and life satisfaction scores were similar. Multilevel growth models demonstrated no serial change in quality-of-life measures except life satisfaction, which decreased significantly after dialysis initiation and remained stable in CKM. In Cox models controlling for comorbidity, Karnofsky performance scale score, age, physical health score, and propensity score, median survival from recruitment was 1317 days in HD patients (mean of 326 dialysis sessions) and 913 days in CKM patients. CONCLUSIONS: Patients choosing CKM maintained quality of life. Adjusted median survival from recruitment was 13 months shorter for CKM patients than HD patients.

Survival of elderly patients with stage 5 CKD: comparison of conservative management and renal replacement therapy.

BACKGROUND: Elderly patients with end-stage renal disease and severe extra-renal comorbidity have a poor prognosis on renal replacement therapy (RRT) and may opt to be managed conservatively (CM). Information on the survival of patients on this mode of therapy is limited. METHODS: We studied survival in a large cohort of CM patients in comparison to patients who received RRT. RESULTS: Over an 18-year period, we studied 844 patients, 689 (82%) of whom had been treated by RRT and 155 (18%) were CM. CM patients were older and a greater proportion had high comorbidity. Median survival from entry into stage 5 chronic kidney disease was less in CM than in RRT (21.2 vs 67.1 months: P < 0.001). However, in patients aged > 75 years when corrected for age, high comorbidity and diabetes, the survival advantage from RRT was ~ 4 months, which was not statistically significant. Increasing age, the presence of high comorbidity and the presence of diabetes were independent determinants of poorer survival in RRT patients. In CM patients, however, age > 75 years and female gender independently predicted better survival. CONCLUSIONS: In patients aged > 75 years with high extra-renal comorbidity, the survival advantage conferred by RRT over CM is likely to be small. Age > 75 years and female gender predicted better survival in CM patients. The reasons for this are unclear.

Residual renal function improves outcome in incremental haemodialysis despite reduced dialysis dose.

BACKGROUND AND METHODS: The importance of residual renal function is well recognized in peritoneal dialysis but its role in haemodialysis (HD) has received much less attention. We studied 650 incident patients in our incremental high-flux HD programme over a 15-year period. Target total Kt/V urea (dialysis plus residual renal) was 1.2 per session and monitored monthly. Renal urea clearance (KRU) was estimated 1-3 monthly. RESULTS: KRU declined during the first 5 years of HD from 3.1 +/- 1.9 at 3 months to 0.9 +/- 1.2 ml/min/1.73 m(2) at 5 years. The percentage of patients with KRU >or= 1 ml/min at these time points was 85% and 31%, respectively. Patients with KRU >or= 1 ml/min had a significantly lower mean creatinine (all time points), ultrafiltration requirement (all time points) and serum potassium (6, 12, 36 and 48 months). Nutritional parameters were also significantly better in respect to nPCR and serum albumin (6, 12, 24 and 36 months). Patients with KRU >or= 1 ml/min had significantly lower erythropoietin requirements and erythropoietin resistance indices (12, 24, 36 and 48 months). Mortality was significantly lower in patients with a KRU >or= 1 at 6, 12 and 24 months after HD initiation, this benefit being maintained after correcting for albumin, age, comorbidities, HDF use and renal diagnosis. Our unique finding was that these benefits occurred despite those with KRU >or= 1 ml/min having a significantly lower dialysis Kt/V at all time points. CONCLUSION: The associations demonstrated suggest that residual renal function contributes significantly to outcome in HD patients and that efforts to preserve it are warranted. Comparative outcome studies should be controlled for residual renal function.

Kt/V underestimates the hemodialysis dose in women and small men.

Current guidelines suggest a minimum Kt/V of 1.2 for three weekly hemodialysis sessions; however, using V as a normalizing factor has been questioned. Parameters such as weight(0.67) (W(0.67)) and body surface area (BSA) that reflect the metabolic rate may be preferable. To determine this, we studied 328 hemodialysis patients (221 male) with a target Kt/V of 1.2. Using this relationship and the individual's Watson Volume, we calculated the Kt, Kt/BSA, and Kt/W(0.67) equivalent to the target and measured the effects of body size and gender on these parameters for each patient. The target corresponded to a range of equivalent Kt/BSA and Kt/W(0.67) each significantly higher in males than females and in larger than smaller males. V/BSA and V/W(0.67), the conversion factors of Kt/V to Kt/BSA and Kt/W(0.67) respectively, were significantly greater in males than females and heavier than lighter men. Our study shows that if Kt/BSA and Kt/W(0.67) reflect the true required dose, prescribing a target Kt/V of 1.2 would underestimate this in females and in small males. Further work is required to develop clinical outcome-based adequacy targets.

Relative importance of residual renal function and convection in determining beta-2-microglobulin levels in high-flux haemodialysis and on-line haemodiafiltration.

BACKGROUND: Convective blood purification improves beta(2)-microglobulin (beta(2)M) removal and may delay the onset of dialysis-related amyloidosis. We assessed the differential effects of high-flux haemodialysis (HD) and on-line haemodiafiltration (HDF) on plasma beta(2)M levels, given the enhanced convective capability of HDF. METHODS: We measured pre-dialysis beta(2)M levels in 297 patients in a programme employing both high-flux HD and HDF, then analysed the relationship of beta(2)M to modality and other variables. RESULTS: Independent determinants of plasma beta(2)M levels were residual renal function, age, HD vintage, and C-reactive protein load, but not the patient's predominant modality (high-flux HD or HDF). Patients with KRU levels <0.5 ml/min had significantly higher beta(2)M levels than patients with KRU between 0.5 and 1 ml/min. CONCLUSIONS: Residual renal function is of overriding importance as a determinant of beta(2)M levels in HD patients and may supersede enhanced convective clearance by HDF. Beneficial effects extend to very low levels of residual renal function.

A dramatic reduction of normalized protein catabolic rate occurs late in the course of progressive renal insufficiency.

BACKGROUND: Spontaneous reduction in dietary protein intake is a recognized feature of severe renal failure, and previous studies have suggested that this may occur at an early stage of renal functional decline. METHODS: We examined the effects of progressive renal insufficiency on the normalized protein catabolic rate (nPCR) in 1282 patients (mean age 55.8+/-15.5 years; 60.4% male) over a 7 year period. All values of nPCR (n = 5082) obtained before commencement of dialysis were included. A total of 361 (28.2%) patients later developed end-stage renal failure and were started on dialysis. RESULTS: Cross-sectional analysis showed nPCR being significantly less at lower creatinine clearance. Mean nPCR was 1.17+/-0.31 at a clearance >50, 1.04+/-0.27 at 25-50, 0.93+/-0.21 at 10-25 and 0.74+/-0.18 at <10 ml/min. Mean nPCR in each clearance group was different from that in all other groups (P<0.001 in all cases). When nPCR was studied longitudinally in relation to time of initiation of dialysis, the fall in nPCR only became significant in the 3 months preceding initiation. Curve fitting suggested a two-phase exponential association between nPCR and renal function, a gentle decline of nPCR in mild and moderate renal failure culminating in a dramatic decline when CrCl reached 15 ml/min and weekly Kt/V(urea) 2.5. nPCR at dialysis initiation predicted survival on dialysis even when corrected for age, diabetes and non-renal co-morbid load. However, it was no longer significant when residual renal function was included in the model. The group initiating dialysis with a normal nPCR maintained this throughout the first 3 years on dialysis whilst the group initiating with a low nPCR, though improving initially, continued to have significantly lower nPCR levels throughout follow-up than their normal nPCR counterparts. CONCLUSION: A significant reduction of nPCR occurs late in progressive renal insufficiency and may predict the need for dialysis initiation. nPCR levels <0.8 at initiation predict future low nPCR levels and mortality on dialysis. The correlation between nPCR and CrCl in early renal insufficiency may be partly artefactual.

Residual renal function: considerations on its importance and preservation in dialysis patients.

Residual renal function (RRF) remains important even after commencement of dialysis. Its role in the adequacy of peritoneal dialysis (PD) is well recognized and is increasingly utilized in incremental PD regimes, but it is also vitally important in hemodialysis (HD) patients, in whom it, as in PD patients, may improve survival. It may allow for a reduction in the duration of HD sessions. It reduces the need for dietary and fluid restrictions in both PD and HD patients. Other contributions include improved middle molecule clearance, better hemoglobin, phosphate, potassium, and urate levels, enhanced nutritional status and quality of life scores, and better outcomes in pregnancy. On the negative side, hypoalbuminemia may be prolonged in patients with persistent nephrotic-range proteinuria. Contrary to popular belief, RRF does not necessarily decline rapidly with the initiation of HD. PD may be better than HD in preserving RRF, although this difference may not persist if biocompatible membranes, bicarbonate buffer, and ultrapure water are used. Nocturnal ambulatory peritoneal dialysis (APD) patients may fare worse than continuous ambulatory peritoneal dialysis (CAPD) patients. RRF can be adversely affected by angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides, and radiocontrast agents. Diuretics can help maintain fluid balance but not RRF.

Identical decline of residual renal function in high-flux biocompatible hemodialysis and CAPD.

BACKGROUND: Patients on conventional hemodialysis lose residual renal function more rapidly than patients on continuous ambulatory peritoneal dialysis (CAPD). The effect of dialysis using synthetic membranes and ultrapure water is less clear. METHODS: The decline of urea clearance was compared in a cohort of 475 incident end-stage renal failure patients who received treatment with CAPD (N=175) or hemodialysis (HD) utilizing high-flux polysulphone membranes, ultrapure water, and bicarbonate as the buffer (N=300). RESULTS: CAPD patients were significantly younger, fitter (lower comorbidity severity score), less dependent (higher Karnofsky performance score) and less likely to have presented late than HD patients. There was no difference in the mean urea clearance in each group at dialysis initiation, or at any 6-month time point during the ensuing 48 months. This was true even after exclusion of patients who had died in the first year after initiation, those transferred to another dialysis modality, or those who had been transplanted. Only age and chronic interstitial disease predicted retention of urea clearance at one year. The rate of decline of urea clearance was similar in pre- and post-dialysis initiation phases, though there may have been a step-decline of about 2 mL/min at initiation, which requires further investigation. CONCLUSIONS: In hemodialysis using high-flux biocompatible membranes and ultrapure water, residual renal function declines at a rate indistinguishable from that in CAPD. This may have important implications, since preservation of residual renal function has major benefits and is a valid therapeutic goal.