Shahid M. Chandna

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.

Choosing not to dialyse: evaluation of planned non-dialytic management in a cohort of patients with end-stage renal failure.

Objectives: To study factors influencing the recommendation for palliative (non-dialytic) treatment in patients approaching end-stage renal failure and to study the subsequent outcome in patients choosing not to dialyse. Design: Cohort study of patients approaching end-stage renal failure who underwent multidisciplinary assessment and counselling about treatment options. Recruitment was over 54 months, and follow-up ranged from 3 to 57 months. Groups were defined on the basis of the therapy option recommended (palliative or renal replacement therapy). Setting: Renal unit in a district general hospital serving a population of about 1.15 million people. Subjects: 321 patients, mean age ± SD 61.5 ± 15.4 years (range: 16–92), 57% male, 30% diabetic. Main Outcome Measures: Survival, place of death (hospital or community). Results: Renal replacement therapy was recommended in 258 patients and palliative therapy in 63 (19.6%). By logistic regression analysis, patients recommended for palliative therapy were more functionally impaired (modified Karnofsky scale), older and more likely to have diabetes. The comorbidity severity score was not an independent predictor. Thirty-four patients eventually died during palliative treatment, 26 of whom died of renal failure. Ten patients recommended for palliative treatment opted for and were treated by dialysis. Median survival after dialysis initiation in these patients (8.3 months) was not significantly longer than survival beyond the putative date of dialysis initiation in palliatively treated patients (6.3 months). 65% of deaths occurring in dialysed patients took place in hospital compared with 27% in palliatively treated patients (p = 0.001). Conclusions: In high-risk, highly dependent patients with renal failure, the decision to dialyse or not has little impact on survival. Dialysis in such patients risks unnecessary medicalisation of death.

Is there a rationale for rationing chronic dialysis? A hospital based cohort study of factors affecting survival and morbidity

Abstract Objectives: To determine factors influencing survival and need for hospitalisation in patients needing dialysis, and to define the potential basis for rationing access to renal replacement therapy. Design: Hospital based cohort study of all patients starting dialysis over a 4year recruitment period (follow up 15-63months). Groups were defined on the basis of age, comorbidity, functional status, and whether dialysis initiation was planned or unplanned. Setting: Renal unit in a district general hospital, which acts as the main renal referral centre for four other such hospitals and serves a population of about 1.15million people. Subjects: 292 patients, mean age 61.3years (18-92years, SD 15.8), of whom 193(66%) were male, and 59(20%) were patients with diabetes. Dialysis initiation was planned in 163(56%) patients and unplanned in 129(44%). Main outcome measures: Overall survival, 1year survival, and hospitalisation rate. Results: Factors affecting survival in the Coxs proportional hazard model were Karnofsky performance score at presentation (hazard ratio 0.979,95% confidence interval 0.972to 0.986), comorbidity severity score (1.240,1.131to 1.340), age (1.036,1.018to 1.054), and myeloma (2.15,1.140to 4.042). The Karnofsky performance score used 3months before presentation was significant (0.970,0.956to 0.981), as was unplanned presentation in this model (1.796,1.233to 2.617). Using these factors, a high risk group of 26patients was defined, with 19.2% 1year survival. Denying dialysis to this group would save 3.2% of the total cost of the chronic programme but would sacrifice five long term survivors. Less rigorous definition of the high risk group would save more money but lose more long term survivors. Conclusions: Severity of comorbid conditions and functional capacity are more important than age in predicting survival and morbidity of patients on dialysis. Late referral for dialysis affects survival adversely. Denial of dialysis to patients in an extremely high risk group, defined by a new stratification based on logistic regression, would be of debatable benefit.

Reviews: 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.

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 individuals 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 patients 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.

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.