Is the measurement of tissue advanced glycosylation products by skin autofluorescence associated with mortality in patients treated by peritoneal dialysis?

BACKGROUND: Advanced glycosylated end-products (AGEs) have been shown to cause cardiovascular disease, and tissue AGE accumulation can be measured by skin autofluorescence (SAF). AGEs are cleared by the kidney, and thus accumulate in dialysis patients. However, as the results of SAF measurements in peritoneal dialysis patients (PD) have been ambiguous, we examined the association between mortality and SAF. METHODS: We reviewed SAF measurements in PD patients attending a university associated PD program, along with standard measurements of dialysis adequacy and peritoneal membrane function. RESULTS: We studied 341 prevalent PD patients, 61.9% male, mean age 61.2 ± 16 years, and 31.4% of all patients died during a median follow-up of 27.2 (23.3-36.3) months. Patients who died were older, mean age 72 ± 10.5 years, were more often diabetic (60.7%), and had higher median SAF 3.8 (3.2-4.5) AU. On logistic regression, mortality was independently associated with age (odds ratio (OR) 1.1 (95% confidence limits 1.06-1.16), diabetes OR 10.1 (3.1-33.4), SAF OR 3.3 (1.8-6.2), all p < 0.001, and male gender OR 5.2 (1.6-17.4), p = 0.007; and negatively associated with weight OR 0.91 (0.86-0.95), p < 0..001, normalised nitrogen appearance rate (nPNA) OR 0.05 (0.01-0.4), p = 0.005 and mean arterial blood pressure (MAP) OR 0.96 (0.93-0.96), p = 0.03. CONCLUSIONS: In this observational study, SAF was independently associated with mortality. However, other factors were also associated with mortality, including age, diabetes and malnutrition which have all been reported to affect SAF measurements. Thus, the additional predictive value of measuring SAF compared to standard risk factors for mortality remains to be determined.

Change in appendicular lean mass in patients established on peritoneal dialysis as measured by dual x-ray absorptiometry (DXA) scanning.

BACKGROUND/OBJECTIVES: Peritoneal dialysis (PD) patients are at increased risk of malnutrition and cachexia, definitions of which include weight loss. However, PD patients can absorb glucose from the dialysate and loss of muscle mass may be overlooked by fat weight gain. As such, we wished to review changes in body composition in prevalent PD patients. SUBJECTS/METHODS: We compared changes in body composition measured by dual x-ray absorptiometry (DXA) in adult PD patients, and calculated glucose absorption based on 24-h collections of PD dialysate. RESULTS: Overall, 73 prevalent PD patients, 60.3% male, mean age 62.5 ± 16.4 years, had DXA scans a median of 24 (15-27) months apart. Weight did not change (70.7 ± 16.8 vs. 70.9 ± 16.8 kg), with a median 198 (88-295) mmol glucose absorbed/day. Appendicular lean mass (ALM) decreased in most of the male (59%) and female (52%) patients, and the change in ALM was negatively associated with the change in percentage body fat mass (%BFM) r = -0.54, p < 0.001. Overall, 56 patients (76.7%) were admitted to hospital with intercurrent illnesses. Women who lost ALM and gained %BFM had more hospital admissions and those with an increase in %BFM had more admissions due to PD peritonitis while, in males, these outcomes were not seen. CONCLUSION: Although overall weight did not change, the majority of PD patients lost ALM, and this loss of muscle mass was masked by a gain in fat mass. Definitions of malnutrition and cachexia, which include unintentional weight loss criteria will underestimate the prevalence of PD patients with loss of muscle mass.

Cardiac arrhythmia during early-week and mid-week dialysis in hemodialysis patients.

Data on cardiac arrhythmia and electrolyte changes during the dialysis cycle have been limited. Fifty-two hemodialysis (HD) patients underwent 48-h Holter monitoring during early-week and mid-week HD sessions. Pre-HD and post-HD blood samples were collected in both HD sessions. The 48-h Holter data were divided into five phases: (1) 4-h during the early-week HD (HD1), (2) 12-h post-HD1, (3) 16-h period between Phases 2 and 4 (used as the patient's baseline electrocardiography [ECG]), (4) 12-h pre-HD2 phase, and (5) 4-h during the mid-week HD (HD2). The patients' mean age was 68.54 ± 13.37 years. We found that the dialysate-to-serum[K] gradient and changes of S[K] were significantly higher in HD1 than in HD2, as well as changes of S[Mg]. There were no significant ECG changes during the 4-h HD1 and HD2 when compared with the baseline ECG. Phase 2 of Holter ECG was the most common phase that showed significant changes (increased QT interval dispersion (QTD), increased ventricular events, increased number of premature ventricular contractions, ST elevation and ST depression), which was contributed from the dialysate[K] 2 mmol/L subgroup, but not the dialysate[K] 3 mmol/L subgroup. In the subgroup of patients with a high ultrafiltration rate (UFR; mean UFR ≥10 mL/kg/h), there were significantly increased ventricular events and ST-segment changes in Phase 2. In conclusion, ECG changes were associated with the dialysis cycle, significantly in the 12-h after early-week HD sessions. These may be associated with low dialysate[K] or high dialysate-to-S[K] gradient, high ultrafiltration rate and duration of the interdialytic interval.

Comparison between standard single chamber versus dual chamber low glucose degradation product peritoneal dialysis fluids.

Dual chamber (DC) peritoneal dialysis (PD) dialysates contain fewer glucose degradation products (GDPs), so potentially reducing advanced glycosylation end products (AGEs), which have been reported to increase inflammation and cardiovascular risk. We wished to determine whether use of DC dialysates resulted in demonstrable patient benefits. Biochemical profiles, body composition, muscle strength, and skin autofluorescence measurements of tissue AGEs (SAF) were compared in patients using DC and standard single chamber dialysates. We studied 263 prevalent PD patients from 2 units, 62.4% male, mean age 61.8 ± 16.1 years, 78 (29.7%) used DC dialysates. DC patients were younger (55.9 ± 16.4 vs. 64.2 ± 15.4 years), and more had lower Davies comorbidity score (median 1 (0-1) vs. 1 (0, 2)), slower peritoneal transport (D/P creatinine 0.67 ± 0.12 vs. 0.73 ± 0.13), greater extracellular water-to-total body water (ECW/TBW) ratio (0.46 ± 0.05 vs. 0.42 ± 0.06), all P < .001, whereas there were no differences in the duration of PD (median (IQR) 19 (8-32) vs. 14 (8-23) months), residual renal function (Kt/Vurea 0.71 ± 0.71 vs. 0.87 ± 0.82), urine volume (642 (175-1200) vs. 648 (300-1200) mL/day), hand grip strength (26.9 ± 10.5 vs. 24.9 ± 10.7 kg), C-reactive protein (4(1-10) vs. 4(2-12) mg/L), and SAF (median 3.60 (3.02, 4.40) vs. 3.50 (3.00, 4.23)) AU. In our cross-sectional observational study, we were not able to show a demonstrable advantage for using low GDP dialysates over conventional glucose dialysates, in terms of biochemical profiles, residual renal function, muscle strength, or tissue AGE deposition. More patients using low GDP dialysates were slower peritoneal transporters with higher ECW/TBW ratios.

Comparison of skin autofluorescence, a marker of tissue advanced glycation end-products in the fistula and non-fistula arms of patients treated by hemodialysis.

Advanced glycosylation end-products (AGEs) are reported to be a risk factor for cardiovascular mortality in hemodialysis (HD) patients. As serum AGEs can change with dialysis, measurement of AGEs deposited in the skin by autofluorescence (SAF) is now a recognized method of measuring AGEs. An arteriovenous fistula (AVF) is the preferred way to access blood in HD patients, and as the creation of an AVF changes blood flow distribution in the arm, we wished to determine whether this affected SAF deposition in the skin. SAF was measured using the AGE reader, which directs ultraviolet light at an intensity range of 300-420 nm (peak 370 nm) in the arms of HD patients dialyzing with an AVF. We measured SAF in 267 patients, 60.3% male, 46.1% diabetic, median duration of dialysis 34.7 (15.1-64.2) months with AVF. The median SAF was lower in the AVF arm (median 3.4 (2.9-4.2) vs. 3.7 (3.2-4.5) AU, P < .001), and for the 160 patients with an upper arm AVF (3.5 (2.9-4.3) vs. 3.8 (3.2-4.5) AU, P < .001), but not for the 107 patients dialyzing with a forearm AVF ((3.4 (2.8-4.2) vs. 3.6 (3.0-4.5) AU, P = .085). Blood flow was greater for upper arm AVF compared to forearm AVFs (1190 (770-1960) vs. (930 (653-1250) mL/min, P = .007), but there was no association between blood flow and SAF (P > .05). AVF alters blood flow in the arm, and we found that SAF measurements were lower in the arm with AVF. We suggest that SAF measurements are made in the non-AVF arm.

Reducing the risk of intradialytic hypotension by altering the composition of the dialysate.

Hypotension is the most common complication of outpatient hemodialysis sessions, with a reported prevalence of 4% to 31%, depending on which definition has been used and whether patients are symptomatic and nursing interventions were required. Dialysis centers which mix the dialysate in the dialysis machine have the opportunity to individualize the composition of the dialysate for patients. This permits a choice of dialysate sodium, potassium, calcium, magnesium, bicarbonate, acetate, and citrate concentrations and temperature. Studies have reported a higher intradialytic systolic blood pressure and fewer episodes of intradialytic hypotension when using a higher dialysate sodium, calcium, magnesium concentrations and lower temperature, but no clinical advantage for changing the potassium, bicarbonate, or citrate for acetate concentrations. The introduction of newer technology allowing real time measurements of plasma electrolyte concentrations will potentially allow changing the dialysate composition to reduce the risk of intradialytic hypotension without increasing the risk of positive electrolyte balances.

Comparison of measuring serum osmolality and equations estimating osmolality in peritoneal dialysis patients.

The osmolar gap increases with kidney failure. A number of equations have been proposed to calculate serum osmolality, allowing determination of the osmolar gap by comparison with measured osmolality. As glucose and icodextrin absorption can potentially interfere with the laboratory measurement of serum sodium, a key component in equations calculating osmolality, we reviewed the performance of 14 equations used to calculate serum osmolality compared to the measurement of serum osmolality in 144 patients with peritoneal dialysis (PD); 81 (56.3%) males, 76 (52.5%) diabetics, mean age of 64.4 ± 16.3 years, 115 (79.9%) prescribed icodextrin and 38 (26.4%) 22.7 g/L glucose dialysates. Measured serum osmolality was 311 (304-320) mosmo/kg (mmol/kg), whereas calculated osmolality for the 14 equations ranged from a median of 274 (269-284) mosmo/kg to 307 (300-316) mosmo/kg. Bland-Altman mean bias showed that measured serum osmolality was greater than the calculated osmolality ranging from 4.0 mosmo/kg to 36.2 mosmo/kg between the 14 equations, with wide 95% limits of agreement (LoA) ranging from -27.1 mosmo/kg to 19.4 mosmo/kg and from -58.5 mosmo/kg to -13.8 mosmo/kg. Only 2 of the 14 equations gave a mean osmolar gap of <10 mosmo/kg and showed no systematic bias, median serum osmolality of 307 (300-316) and 303 (298-312) mosmo/kg, Spearman ρ of 0.57, 0.62, both p < 0.001, respectively. Our study would suggest that only 2 of the 14 equations we compared with measured serum osmolality showed no systematic bias, but still had too great a bias to be useful in clinical practice. As such we propose a new equation to calculate serum osmolality in patients with PD.