Elvia García-López

An update on peritoneal dialysis solutions

Peritoneal dialysis (PD) has achieved its current position as the most commonly used home-based dialysis therapy—and with patient survival equal to that seen with hemodialysis—despite the use of glucose-based dialysis solutions with high concentrations of glucose, glucose degradation products and lactate, high osmolality, and low pH, features that are harmful both for the peritoneum and the patient. Newer PD solutions with alternative buffers, a higher pH and fewer glucose degradation products, or ones that contain icodextrin or amino acids as osmotic agents, have been introduced in many countries and have been shown to improve peritoneal membrane health and viability. Icodextrin solution enhances fluid and sodium removal, and the once-daily use of icodextrin and/or amino acid solutions can lessen the harmful effects caused by the exposure of the peritoneal membrane to glucose. However, whether the newer PD solutions improve patient survival over the older solutions is not clear. Use of PD therapy, with or without the newer PD solutions, is associated with an improvement in patient survival that is equivalent to that obtained with hemodialysis. Therefore, the conventional glucose-based solutions—despite their known negative features—continue to have a well-established role in PD therapy, particularly in the many countries where the newer PD solutions are not easily available.

Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study

Patients with chronic kidney disease (CKD) have signs of genomic instability and, as a consequence, extensive genetic damage, possibly due to accumulation of uraemic toxins, oxidative stress mediators and other endogenous substances with genotoxic properties. We explored factors associated with the presence and background levels of genetic damage in CKD. A cross-sectional study was performed in 91 CKD patients including pre-dialysis (CKD patients; n = 23) and patients undergoing peritoneal dialysis (PD; n = 33) or haemodialysis (HD; n = 35) and with 61 healthy subjects, divided into two subgroups with the older group being in the age range of the patients, serving as controls. Alkaline comet assay and cytokinesis-block micronucleus assay in peripheral blood lymphocytes were used to determine DNA and chromosome damage, respectively, present in CKD. Markers of oxidative stress [malondialdehyde (MDA), advanced glycation end products (AGEs), thiols, advanced oxidation protein products and 8-hydroxy-2′-deoxyguanosine] and markers of inflammation (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were also measured. Micronucleus (MN) frequency was significantly higher (P < 0.05) in the CKD group (46±4‰) when compared with the older control (oC) group (27.7±14). A significant increase in MN frequency (P < 0.05) was also seen in PD patients (41.9±14‰) versus the oC group. There was no statistically significant difference for the HD group (29.7±15.6‰; P = NS) versus the oC group. Comet assay data showed a significant increase (P < 0.001) of tail DNA intensity in cells of patients with CKD (15.6±7%) with respect to the total control (TC) group (11±1%). PD patients (14.8±7%) also have a significant increase (P < 0.001) versus the TC group. Again, there was no statistically significant difference for the HD group (12.5±3%) compared with the TC group. Patients with MN values in the upper quartile had increased cholesterol, triglycerides, AGEs and MDA levels and lower albumin levels. Multiple logistic regression analysis showed that male gender, diabetes and treatment modality were independently associated with higher levels of DNA damage. Our results suggest that oxidative stress, diabetes, gender and dialysis modality in CKD patients increased DNA and chromosome damage. To confirm these data, prospective clinical trials need to be performed.

Double-dose icodextrin to increase ultrafiltration in PD patients with inadequate ultrafiltration.

recommendations: 2010 update. Perit Dial Int 2010; 30:393–423. 2. Duranay M, Kanbay M, Turgut F, Altay M, Akcay A. Comparison of incidence of peritonitis between peritoneal dialysis solution types. nephron Clin Pract 2007;106:c57–60. 3. Rocklin MA, Teitelbaum I. Noninfectious causes of cloudy peritoneal dialysate. Semin Dial 2001;14:37–40. 4. Nouri–Majalan N, Najafi I, Sanadgol H, Ganji MR, Atabak S, Hakemi M, et al. Description of an outbreak of acute sterile peritonitis in Iran. Perit Dial Int 2010;30:19–22. doi: 10.3747/pdi.2010.00264

Threefold Peritoneal Test of Osmotic Conductance, Ultrafiltration Efficiency, and Fluid Absorption

♦ Background: Fluid removal during peritoneal dialysis depends on modifiable factors such as tonicity of dialysis fluids and intrinsic characteristics of the peritoneal transport barrier and the osmotic agent—for example, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption. The latter parameters cannot be derived from tests of the small-solute transport rate. We here propose a simple test that may provide information about those parameters. ♦ Methods: Volumes and glucose concentrations of drained dialysate obtained with 3 different combinations of glucose-based dialysis fluid (3 exchanges of 1.36% glucose during the day and 1 overnight exchange of either 1.36%, 2.27%, or 3.86% glucose) were measured in 83 continuous ambulatory peritoneal dialysis (CAPD) patients. Linear regression analyses of daily net ultrafiltration in relation to the average dialysate-to-plasma concentration gradient of glucose allowed for an estimation of the osmotic conductance of glucose and the peritoneal fluid absorption rate, and net ultrafiltration in relation to glucose absorption allowed for an estimation of the ultrafiltration effectiveness of glucose. ♦ Results: The osmotic conductance of glucose was 0.067 ± 0.042 (milliliters per minute divided by millimoles per milliliter), the ultrafiltration effectiveness of glucose was 16.77 ± 7.97 mL/g of absorbed glucose, and the peritoneal fluid absorption rate was 0.94 ± 0.97 mL/min (if estimated concomitantly with osmotic conductance) or 0.93 ± 0.75 mL/min (if estimated concomitantly with ultrafiltration effectiveness). These fluid transport parameters were independent of small-solute transport characteristics, but proportional to total body water estimated by bioimpedance. ♦ Conclusions: By varying the glucose concentration in 1 of 4 daily exchanges, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption could be estimated in CAPD patients, yielding transport parameter values that were similar to those obtained by other, more sophisticated, methods.

Cardiovascular and Renal Effects of Bromocriptine in Diabetic Patients with Stage 4 Chronic Kidney Disease

Objective. The objective of this study was to investigate the effect of bromocriptine (BEC) on left ventricular mass index (LVMI) and residual renal function (RRF) in chronic kidney disease (CKD) patients with type 2 diabetes (T2D). Research Design and Methods. A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day) and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day). Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP) plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels. Results. Both BEC and PBO groups decreased blood pressure—but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC (0.54 ± 0.15 to 0.32 ± 0.17 pg/mL) and increased in PBO (0.37 ± 0.15 to 0.64 ± 0.17 pg/mL). Creatinine clearance did not change in the BEC group and decreased in the PBO group. Conclusions. BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged.

Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients

Background A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients. Methods Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 μmol/L), NE (1.0 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L), and from five nonobese and normotensive controls treated with DA (1 μmol/L), NE (1 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L). Results A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. Conclusion These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.

Reaching Targets for Mineral Metabolism Clinical Practice Guidelines and Its Impact on Outcomes Among Mexican Chronic Dialysis Patients

BACKGROUND AND AIMS An increasing number of studies have been published concerning meeting targets of clinical guidelines for different aspects of the diagnosis and treatment of patients with end-stage renal disease. Most of these studies have shown that guideline recommendations are not always satisfied, and results outside target limits have been associated with high rates of mortality and morbidity. The objective of this study was to analyze the frequency of reaching mineral and bone metabolism-related guideline targets and its impact on clinical outcomes in Mexican chronic dialysis patients. METHODS A cohort of prevalent peritoneal dialysis (PD) and hemodialysis (HD) patients were analyzed at baseline and followed for at least 16 months. Patients were on continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD), and HD and contracted HD modalities where patients received HD sessions outside institution facilities. RESULTS We studied 753 patients. The percentage of patients within target limits for phosphorus was 35%, for calcium 32%, and for PTH 12%. The most frequent pattern was hyperphosphatamia, hypercalcemia, and low PTH. This was even more frequent in CAPD patients, probably due to the high percentage of diabetic patients. Hypercalcemia was found as an independent risk factor for mortality. CONCLUSIONS The most important results suggest that guideline recommendations are not usually satisfied and that hypercalcemia, in addition to other traditional risk factors, is associated with high mortality rates. The study also detected some opportunities to improve the quality of treatment by reducing the calcium content of dialysis solutions and reducing the use of calcium carbonate as a phosphate binder.

ULTRAFILTRATION AND DIALYSIS ADEQUACY WITH VARIOUS DAILY SCHEDULES OF DIALYSIS FLUIDS

Dialysis regimens for continuous ambulatory peritoneal dialysis (CAPD) patients vary with the need for fluid removal, but also because of concerns about the local and systemic consequences of high glucose exposure. The implications of various regimens for dialysis adequacy—that is, fluid and small-solute removal—are not always clear. We therefore analyzed ultrafiltration (UF) and adequacy indices for 4 different combinations of dialysis fluid. Collections of 24-hour dialysate and urine were carried out in 99 patients on CAPD. On 4 separate occasions, each patient performed 4 exchanges in 24 hours, including 3 daily exchanges with 1.36% glucose and 1 night exchange with either 1.36% glucose (G1 schedule), 2.27% glucose (G2 schedule), 3.86% glucose (G3 schedule), or icodextrin (Ico schedule). Weekly, total, and dialysis Kt/V and KT were calculated for both urea and creatinine. The mean values of urea Kt/V and KT were significantly lower for the G1 schedule than for the G3 and Ico schedules. The adequacy indices for overnight application of 3.86% glucose and icodextrin were similar. Using dialysis fluids with 1.36% and 2.27% glucose overnight reduces glucose exposure, but those schedules may provide inadequate UF and small-solute removal in some patients (UF < 1 L daily, Kt/V < 1.7).

DIALYSIS ADEQUACY INDICES AND BODY COMPOSITION IN MALE AND FEMALE PATIENTS ON PERITONEAL DIALYSIS

♦ Objectives: Creatinine clearance scaled to body surface area (BSA) and urea KT/V normalized to total body water (TBW) are used as indices for peritoneal dialysis (PD) adequacy. We investigated relationships of indices of dialysis adequacy (including KT/V, KT, clearance, dialysate over plasma concentration ratio) and anthropometric and body composition parameters (BSA, TBW, body mass index (BMI), weight, height, fat mass (FM), and fat-free mass (FFM)) in male and female patients on continuous ambulatory peritoneal dialysis. ♦ Methods: Ninety-nine stable patients (56 males) performed four 24-hr collections of drained dialysate for four dialysis schedules with three daily exchanges of glucose 1.36% and one night exchange of either: 1) glucose 1.36%, 2) glucose 2.27%, 3) glucose 3.86% or 4) icodextrin 7.5%. ♦ Results: KT and dialysate over plasma concentration ratio, CD/CP, for urea and creatinine were similar for males and females and, in general, did not depend on body-size parameters including V (= TBW), which means that the overall capacity of the transport system in females and males is similar. However, after normalization of KT to V or 1.73/BSA yielding KT/V and creatinine clearance, Cl(1.73/BSA), respectively, the normalized indices were substantially higher in females than in males and correlated inversely with body-size parameters, especially in males. ♦ Conclusions: As KT/V depends strongly on body size, treatment target values for KT/V should take body size and therefore also gender into account. As KT is less influenced by body size, body composition and gender, KT should be considered as a potential auxiliary index in PD.

Effect of Icodextrin on Heart Rate Variability in Diabetic Patients on Peritoneal Dialysis

♦ Introduction: Spectral analysis of heart rate variability is a noninvasive method for evaluating autonomic cardiovascular dysfunction under various clinical conditions, such as in dialysis patients, in whom an imbalance between the sympathetic and parasympathetic nervous system appears to be an important risk factor for sudden cardiovascular death and arrhythmia. ♦ Objective: We compared the effect of icodextrin-based dialysis solution, an option that allows for better metabolic and fluid overload control, with that of glucose-based dialysis fluid on sympathetic and parasympathetic activity in the heart, as assessed by heart rate variability, in diabetic patients on peritoneal dialysis (PD). ♦ Methods: This secondary analysis uses data from a randomized controlled trial in diabetic PD patients with high or high-average peritoneal transport using icodextrin-based (ICO group, n = 30) or glucose-based (GLU group, n = 29) solutions for the long dwell. All patients underwent 24-hour electrocardiographic Holter monitoring at baseline, and at 6 and 12 months of follow-up. ♦ Results: We observed no significant differences between the groups in most of the variables analyzed, although values were, in general, below reference values. In the ICO group, total power and both low- and high-frequency power in normalized units increased, but the percentage of RR intervals with variation of more than 50 ms declined over time; in the GLU group, all those values declined. Plasma catecholamine levels were higher at baseline and declined over time. ♦ Conclusions: These results indicate a partial recovery of sympathetic activity in the ICO group, probably because of better extracellular fluid control and lower exposure to glucose with the use of icodextrin-based dialysis solutions.