Jeffrey Perl

Hemodialysis Vascular Access Modifies the Association between Dialysis Modality and Survival

Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD.

Gastrointestinal Adverse Events with Sodium Polystyrene Sulfonate (Kayexalate) Use: A Systematic Review

BACKGROUND Sodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use has been associated with colonic necrosis and other fatal gastrointestinal adverse events. Although the addition of sorbitol to sodium polystyrene sulfonate preparations was previously believed to be the cause of gastrointestinal injury, recent reports have suggested that sodium polystyrene sulfonate itself may be toxic. Our objective was to systematically review case reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. METHODS MEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (1993 to July 27, 2011), bibliographies of identified articles, and websites of relevant drug agencies and professional associations in the United States and Canada were reviewed to identify eligible reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. Causality criteria of the World Health Organization causality assessment system were applied to each report. RESULTS Thirty reports describing 58 cases (41 preparations containing sorbitol and 17 preparations without sorbitol) of adverse events were identified. The colon was the most common site of injury (n=44; 76%), and transmural necrosis (n=36; 62%) was the most common histopathologic lesion reported. Mortality was reported in 33% of these cases due to gastrointestinal injury. CONCLUSIONS Sodium polystyrene sulfonate use, both with and without sorbitol, may be associated with fatal gastrointestinal injury. Physicians must be cognizant of the risk of these adverse events when prescribing this therapy for the management of hyperkalemia.

The Importance of Residual Kidney Function for Patients on Dialysis: A Critical Review

Increasing the dialysis dose has failed to have an impact on the mortality of dialysis patients. In contrast, residual kidney function (RKF) has consistently been a potent predictor of improved survival for both hemodialysis and peritoneal dialysis patients. The benefits of RKF preservation challenge historical concepts of dialysis adequacy that have focused principally on achieving small-solute clearance targets. In this review, we highlight the evidence supporting the impact of RKF on survival and quality of life of dialysis patients and provide a mechanistic framework for this relationship. Current strategies to preserve RKF also are reviewed, emphasizing those used in patients treated with peritoneal dialysis.

Risk of Chronic Dialysis and Death Following Acute Kidney Injury

BACKGROUND Acute kidney injury frequently arises within an acute care hospitalization. Outcomes among acute kidney injury survivors following hospital discharge are poorly documented. METHODS We conducted a population-based cohort study between 1996 and 2006 of all adult patients in Ontario with acute kidney injury who did not require in-hospital dialysis, and who survived free of dialysis ≥30 days after discharge. Those with acute kidney injury (n=41,327) were matched 1:1 to patients without acute kidney injury during their index hospitalization. Matching was by age (±1 year), sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury. The primary outcome was subsequent need for chronic dialysis. The secondary outcomes were all-cause mortality and rehospitalization. RESULTS Mean age was 70 years, and median follow-up was 2 years (maximum 10 years). The incidence of chronic dialysis was 1.78 per 100 person-years among those with acute kidney injury and 0.74 per 100 person-years among unaffected controls (adjusted hazard ratio [HR]; 2.70, 95% confidence interval [CI], 2.42-3.00). Rates also were higher for all-cause mortality (15.34 vs 14.51 per-100 person-years; adjusted HR 1.10; 95% CI, 1.07-1.13) and rehospitalization (44.93 vs 37.18 per 100 person-years; adjusted HR 1.21; 95% CI, 1.18-1.24). CONCLUSION Even when acute dialysis is not required, survivors of acute kidney injury remain at higher risk of receipt of chronic dialysis thereafter. The absolute risk of death was more than 8 times the rate of chronic dialysis.

Peritoneal Protein Clearance and not Peritoneal Membrane Transport Status Predicts Survival in a Contemporary Cohort of Peritoneal Dialysis Patients

BACKGROUND AND OBJECTIVES Fast peritoneal membrane transport status may be due to inflammation or increased peritoneal membrane surface area. We evaluated the ability of peritoneal protein clearance (Pcl) to distinguish fast peritoneal membrane transport status as a consequence of peritoneal membrane inflammation and assess its impact on patient survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients who initiated peritoneal dialysis at our center since January 1998 and had a baseline peritoneal equilibration test, measurement of dialysis adequacy, and 24-h dialysate Pcl were included. Demography, comorbidities, and biochemical data were prospectively collected. Follow-up was until death or the end of the period studied. Multivariate regression analysis identified factors that were associated with Pcl. A Cox proportional hazards model was used to identify factors that were associated with survival. RESULTS A total of 192 patients (56% men, mean age 54.3 +/- 15.3; 32% with diabetes) were included. On univariate analysis, Pcl was negatively correlated with serum albumin and positively correlated with age, dialysate/plasma creatinine ratio (D/Pcr), the presence of peripheral vascular disease, and urine volume. On multivariate analysis, serum albumin, D/Pcr, urine volume, and peripheral vascular disease remained significant. Predictors of mortality were age, comorbidity grade, and Pcl but not D/Pcr. CONCLUSIONS In this cohort, peritoneal transport status no longer predicted survival, whereas Pcl remained a predictor. Increased large-pore protein loss may reflect the severity of underlying cardiovascular disease, portending a poor prognosis for these patients.

The biocompatibility of neutral pH, low-GDP peritoneal dialysis solutions: benefit at bench, bedside, or both?

For patients on peritoneal dialysis (PD), the development of peritonitis, the decline of residual kidney function, and the loss of peritoneal membrane function are central events that affect both patient and technique survival. The use of glucose as the osmotic agent in conventional PD solutions may increase the susceptibility to each of these events. However, its use may also be associated with systemic metabolic perturbations and, in turn, an increase in cardiovascular morbidity. Both in vitro and in vivo evidence suggest that both the local peritoneal and systemic toxicity induced by the use of glucose may be in part mediated by the presence of glucose degradation products (GDPs) coupled with the hyperosmolarity, reduced pH, and use of lactate as the buffer in conventional PD solutions. Therefore, the use of neutral pH, low-GDP (NpHL(GDP)), bicarbonate-buffered PD solutions may represent a promising strategy to attenuate some of these adverse effects. However, the impact of these novel solutions on clinical outcomes remains largely unknown. In this review, we will highlight evidence regarding the biocompatibility of NpHL(GDP) PD solutions, review the utility of current biomarkers in the evaluation of biocompatibility, and discuss the clinical outcome data with these solutions.

Reduced survival and quality of life following return to dialysis after transplant failure: the Dialysis Outcomes and Practice Patterns Study

BACKGROUND Although dialysis after kidney transplant failure (TF) is common, the outcomes of these patients remain unclear. We compared outcomes of TF patients with transplant-naïve (TN) patients wait-listed for kidney transplantation. METHODS We used data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), including laboratory markers and health-related quality of life (HR-QOL). Mortality and hospitalization of participants with one prior TF versus TN patients were compared using the Cox regression analysis. HR-QOL physical and mental component summary scores (PCS and MCS) were examined using linear mixed models, and clinical practices were compared using logistic regression. RESULTS Compared with TN patients (n = 2806), TF patients (n = 1856) were younger (48 versus 51 years, P = 0.003), less likely to be diabetic (18 versus 27%, P < 0.0001) and to use a permanent surgical vascular access {adjusted odds ratio (AOR): 0.85 [95% confidence interval (CI): 0.70-1.03], P = 0.10}, particularly within the first 3 months after TF [AOR 0.45 (0.32-0.62), P < 0.0001]. TF patients also had lower PCS [mean difference -2.56 (-3.36, -1.75), P < 0.0001] but not MCS [-0.42 (-1.34, 0.50), P = 0.37]. All-cause mortality [adjusted hazard ratio (AHR): 1.32 (95% CI: 1.05-1.66), P = 0.02], especially infection-related [AHR 2.45 (95% CI: 1.36-4.41), P = 0.01], was higher among TF patients. CONCLUSIONS TF patients have reduced QOL and higher mortality, particularly due to infections, than TN patients. Interventions to optimize care before and after starting dialysis remain to be identified and applied in clinical practice.

Impact of Dialysis Modality on Survival after Kidney Transplant Failure

BACKGROUND AND OBJECTIVES An increasing number of patients are returning to dialysis after allograft loss (DAGL). These patients are at a higher mortality risk compared with incident ESRD patients. Among transplant-naïve patients, those treated with peritoneal dialysis (PD) enjoy an early survival advantage compared with those treated with hemodialysis (HD), but this advantage is not sustained over time. Whether a similar time-dependent survival advantage exists for PD-treated patients after allograft loss is unclear and may impact dialysis modality selection in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We identified 2110 adult patients who initiated dialysis after renal transplant failure between January 1991 and December 2005 from The Canadian Organ Replacement Register. Multivariable regression analysis was used to evaluate the impact of initial dialysis modality on early (2 years), late (after 2 years), and overall mortality using an intention-to-treat approach. RESULTS After adjustment, there was no difference in overall survival between HD- and PD-treated patients (hazard ratio((HD:PD)), 1.05; 95% confidence interval, 0.85 to 1.31), with similar results seen for both early and late survival. Superior survival was seen in more contemporary cohorts of patients returning to DAGL. CONCLUSIONS The use of PD compared with HD is associated with similar early and overall survival among patients initiating DAGL. Differences in both patient characteristics and predialysis management between patients returning to DAGL and transplant-naive incident dialysis patients may be responsible for the absence of an early survival advantage with the use of PD in DAGL patients.

The renin-angiotensin-aldosterone system in peritoneal dialysis: is what is good for the kidney also good for the peritoneum?

Morphological changes of the peritoneal membrane that occur over time among patients on peritoneal dialysis include fibrosis and neoangiogenesis. While the pathophysiologic mechanisms underlying these changes are not fully understood, the activation of the renin-angiotensin-aldosterone system (RAAS) may have an important role. Components of the RAAS are constitutively expressed within peritoneal mesothelial cells, and are upregulated in the presence of acute inflammation and chronic exposure to peritoneal dialysate. The high glucose concentration, low pH, and the presence of glucose degradation products in peritoneal dialysis solutions have all been implicated in modulation of peritoneal RAAS. Furthermore, activation of the RAAS, as well as the downstream production of transforming growth factor-beta, contributes to epithelial-to-mesenchymal transformation of mesothelial cells, resulting in progressive fibrosis of the peritoneal membrane. This process also leads to increased vascular endothelial growth factor production, which promotes peritoneal neoangiogenesis. Functionally, these changes translate into reduced ultrafiltration capacity of the peritoneal membrane, which is an important cause of technique failure among patients on long-term peritoneal dialysis. This brief review will describe our current state of knowledge about the role of peritoneal RAAS in peritoneal membrane damage and potential strategies to protect the membrane.

Rehospitalizations and Emergency Department Visits after Hospital Discharge in Patients Receiving Maintenance Hemodialysis

Clinical outcomes after a hospital discharge are poorly defined for patients receiving maintenance in-center (outpatient) hemodialysis. To describe the proportion and characteristics of these patients who are rehospitalized, visit an emergency department, or die within 30 days after discharge from an acute hospitalization, we conducted a population-based study of all adult patients receiving maintenance in-center hemodialysis who were discharged between January 1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada. For patients with more than one hospitalization, we randomly selected a single hospitalization as the index hospitalization. Of the 11,177 patients included in the final cohort, 1926 (17%) were rehospitalized, 2971 (27%) were treated in the emergency department, and 840 (7.5%) died within 30 days of discharge. Complications of type 2 diabetes mellitus were the most common reason for rehospitalization, whereas heart failure was the most common reason for an emergency department visit. In multivariable analysis using a cause-specific Cox proportional hazards model, the following characteristics were associated with 30-day rehospitalization: older age, the number of hospital admissions in the preceding 6 months, the number of emergency department visits in the preceding 6 months, higher Charlson comorbidity index score, and the receipt of mechanical ventilation during the index hospitalization. Thus, a large proportion of patients receiving maintenance in-center hemodialysis will be readmitted or visit an emergency room within 30 days of an acute hospitalization. A focus on improving care transitions from the inpatient setting to the outpatient dialysis unit may improve outcomes and reduce healthcare costs.