Giovambattista Virga

Serum Beta-2-Microglobulin Level and Residual Renal Function in Peritoneal Dialysis

In 32 noncirrhotic patients on peritoneal dialysis, mean serum beta 2-microglobulin (s beta 2M) was 26.58 +/- 12.32 mg/l (9.7-63.5). We found a significant correlation between s beta 2M and serum creatinine (sCr; r = 0.760), blood urea nitrogen (BUN; r = 0.573), total creatinine and BUN clearance (r = 0.623 and 0.599, respectively), 24-hour Kt/V (r = 0.638), glomerular filtration rate (r = 0.623), 24-hour urine output (r = 0.669), serum total protein (r = 0.584) (p < 0.01 for all the above r values); beta 2M peritoneal clearance and mass transfer (r = 0.414 and 0.427, respectively; p < 0.05). Our data demonstrate and confirm the contribution of residual renal function in determining s beta 2M levels and it is seemingly more important than beta 2M peritoneal clearance.

Comparison of fast peritoneal equilibration tests with 1.36 and 3.86% dialysis solutions

At present dialysis solutions with different glucose concentrations are used for the peritoneal equilibration test (PET) and Fast-PET in peritoneal dialysis (PD). We compared the results of two Fast-PETs, using 1.36 and 3.86% solutions sequentially in 30 patients on PD treatment, to obtain information on peritoneal transport (D/P-4 h) and ultrafiltration rates. Creatinine, phosphorus and urea D/P-4 h in the two Fast-PETs were not statistically different, unlike those for potassium, beta 2-microglobulin and glucose. The creatinine and phosphorus D/P-4 h values in particular proved to be uninfluenced by the different dialysis solutions. The lack of correlation between the two Fast-PET ultrafiltration values confirmed the difficulty in interpreting this parameter, above all in the case of non-homologous Fast-PETs. We obtained useful indications for comparing different Fast-PET results, but were unable to reach a decisive conclusion regarding the best of the two dialysis solutions for this test.

Hypercalcemia and Insomnia in Hemodialysis Patients

Accessible online at: www.karger.com/journals/nef Dear Sir, We read with great interest the paper by Argiles et al. [1] about a hemodialysis (HD) patient who complained of sweating, pruritus and insomnia, and was irritable and restless. Moderate hypercalcemia (total Ca 2.9 mmol/l) was found and suspected as the cause of these symptoms. He had unintentionally received a dialysate with 1.75 mmol/l Ca and after lowering the Ca concentration in the dialysate (1.75k1.25 mmol/l) clinical manifestations rapidly resolved. In a previous paper about 14 symptoms in HD patients, we reported that insomnia, defined as ‘waking at night and failing to return to sleep’ or ‘not sleeping at all’, had a relation with the midweek predialysis total serum calcium (sCa) [2]. In fact, sCa in patients with absent vs occasional vs constant insomnia were 9.8 (9.6–10.3) vs. 9.9 (9.2–10.3) vs. 10.3 B 0.5, respectively, with a significant statistical difference (p = 0.041: 0–1 vs. 2). This association does not appear to have been reported before. Moreover, of the 15 patients reporting persistent insomnia, 12 (80%) had a predialysis sCa of 110 mg/dl and we defined them as ‘hypercalcemic’ because of a probable mild hypercalcemia during the interdialysis period with regard to the Ca concentration in the dialysate (1.75 for bicarbonate HD and 2.00 mmol/l for acetate-free biofiltration). One year later (June 1998), we changed the Ca concentration in the dialysate (1.75– 2.00k1.25 mmol/l) and after 5 months (November 1998) we reevaluated all our patients with regard to insomnia as well as other uremic symptoms using the same procedure as in the previous study [2]. Results on the comparison between the two evaluations are summarized in table 1. sCa data are expressed as mean B SD or median value (interquartile range) if the distribution was not Gaussian. Insomnia data were available for 73 of 76 and 68 of 70 patients in June 1997 and November 1998, respectively, and the sCa dosage is given for all patients. Nonparametric Mann-Whitney twotailed U test (sCa), Fisher exact test (% of patients with sCa 110 mg/dl) and ̄2 test (absent, occasional, constant insomnia) were used to compare the June 1987 and November 1998 data. The null hypothesis was rejected for all tests with two-tailed · values of !0.05.

Correction of glucose concentration interference on Jaffé kinetic creatinine assay in peritoneal dialysis

Overestimation of creatinine measurement using the Jaffé kinetic method in peritoneal dialysis solutions, due to glucose interference, has been quantified and corrected through the elaboration of linear formulas obtained from 110 recovery and 301 biological tests. The added pure powdered creatinine and enzymatic method were considered as references after proven accuracy. Considering creatinine as well as glucose concentration interference, we obtained correction formulas from multiple regression application. All the computed formulas gave satisfactory corrections but different accuracy levels. The best model in biological samples was: Corrected CR = K1JafféCr + K2Glucose (all values in mg/dl) where K1 = 0.973 and K2 = -0.00035 (Rsq = 0.987, F ratio = 10,945, p = 0.00001). Applying formulas to biological samples there was a drop in accuracy, possibly explained by the presence of numerous unidentified substances in peritoneal dialysis biological samples that can amplify scatter. Every laboratory can reduce the error of the Jaffé kinetic assay by calculating their own correction formula in relation to the method and instrument used, because Jaffé kinetic assay gives different results with different kinetic windows. So, especially when applied to peritoneal dialysis fluid measurements, if a creatinine assay reference method is not available, the correction formula can be applied directly as given. Otherwise the method we have described can be followed with a well-structured creatinine recovery fest to identify and quantify assay interferences.

A New Equation for Estimating Renal Function Using Age, Body Weight and Serum Creatinine

Background: Many formulas have been developed to estimate glomerular filtration rate (GFR). The aim of our study was to propose a new, more reliable equation. Methods: The study considered 530 subjects (training sample) with M/F 280/250, age 57.1 ± 17.4, creatinine clearance (CrCl) 55.2 ± 38.2 (range 2.1–144.0) for the development the new equation. A linear model was used to describe Cr production using serum Cr (sCr), age, and body weight (BW) as variables: (CrCl + b4) · sCr = b1 – (b2 · age) + (b3 · BW) subsequently estimating parameter values by linear least squares, with CrCl as the dependent variable, and 1/sCr, age/sCr, BW/sCr as independent variables. CrCl = {[69.4 – (0.59 · age) + (0.79 · BW)]/sCr} – 3.0 (males) and {[57.3 – (0.37 · age) + (0.51 · BW)]/sCr} – 2.9 (females). A 229-patient renal failure validation sample with M/F 166/63, age 53.0 ± 14.8, GFR 32.0 ± 14.3 (range 4.3–69.8), assessed using iohexol Cl, was considered to compare the Cockcroft-Gault (C-G) and MDRD formulas with the new equation for estimating GFR. Results: The mean % error in GFR estimated by the new equation (+2.3 ± 28.3%) was better than with the C-G and MDRD formulas (+5.2 ± 30.1% and –11.4 ± 25.9%, respectively, p < 0.0005 and p < 0.0001), and so was the mean absolute % error, bordering on statistical significance (19.8 ± 20.3 vs. 21.1 ± 22.0 and 22.4 ± 17.3, p = 0.08 and p < 0.005). The precision was also better (RMSE = 7.89 vs. 8.02 and 9.13). The Bland-Altman test showed no GFR over or underestimation trend (measured ± predicted GFR/2 vs. % error, R2 = 0.001). Conclusions: The new equation appears to be at least as accurate as the C-G and MDRD formulas for estimating GFR.

Verticillium Peritonitis in a Patient on Peritoneal Dialysis

We describe a case of peritonitis due to Verticillium spp. in a 33-year-old farmer on continuous ambulatory peritoneal dialysis (CAPD) for 3 months for end-stage renal failure due to chronic pyelonephritis. The etiologic agent was a hyaline hyphomycete which we report as a new human opportunistic pathogen. The fungus was isolated from the peritoneal fluid culture and from the tip of the catheter; identification was made on the basis of macroscopic and microscopic features. The patient had previously been admitted to our hospital for peritonitis caused by mixed enteric flora and treated for 8 days with intraperitoneal broad-spectrum antibiotic therapy. Five days after discharge he was readmitted for severe abdominal pain and cloudy drainage fluid. Two days of intraperitoneal broad-spectrum antimicrobial therapy produced no clinical improvement. Intravenous fluconazole and oral flucytosine were administered upon identifying the fungus. After another 2 days without improvement, peritoneal dialysis was discontinued and the catheter removed. Antimycotic therapy was continued for 4 days with complete resolution of the peritonitis. The patient chose to start hemodialysis and was discharged in good clinical condition.

Comparison between creatinine-based equations for estimating total creatinine clearance in peritoneal dialysis: a multicentre study

BACKGROUND It is crucial to assess the adequacy of peritoneal dialysis (PD) because of its influence on patient outcome. Collecting dialysate and urine for 24 h can be rather troublesome, so a simple and inexpensive alternative method for rapidly evaluating adequacy in PD would be very useful. Our study aimed to assess the performance of 12 different creatinine (Cr)-based equations commonly used to estimate GFR in predicting total Cr clearance (totCrCL) in PD. METHODS Four Italian dialysis centres enrolled 355 PD patients with 2916 fluid collections. To rank the equations, their accuracy (median absolute percentage error, MAPE), precision (root mean square error, RMSE), agreement (k statistics), sensitivity and specificity (area under ROC curves, AUC, where x = 1 - specificity and y = sensitivity) were calculated with reference to the measured totCrCL. RESULTS The Gates, Virga and 4-MDRD equations showed the best global performance as concerns accuracy (MAPE = 14.1, 16.3, 15.9% respectively), precision (RMSE = 13.2, 13.3, 13.4), agreement (k = 0.425, 0.440, 0.375), sensitivity and specificity (AUC = 0.825, 0.826, 0.820), while the Cockcroft-Gault formula revealed a rather poor reliability. CONCLUSIONS Fluid collection remains the gold standard for assessing PD adequacy. Our study ascertained how 12 Cr-based equations performed in estimating totCrCL in PD patients with a view to enabling the most accurate and precise among them to be chosen for use in approximately assessing totCrCL.

Mortality in the Veneto population on renal replacement therapy.

This section reports survival rates for patients on renal replacement therapy (RRT). The data obtained from the Veneto Dialysis and Transplantation Registry (VDTR) cover the whole population in the region. Patients on RRT alive on 31 December of each year were assumed to be at risk of dying in the following year. Furthermore, time-to-event analysis was used to describe the complete history of patients from when they started RRT until they died, including transitions between the 3 main treatment modalities - hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation. The cohort of patients starting RRT from 1998 to 2010 was followed up until 31 December 2010. Survival rates from the first treatment to death were calculated according to the life table method. Relative survival and excess mortality rates were estimated according to the Ederer II method. A multistate model was used to describe changes in a patients condition (changes of treatment, or death) over time. Among prevalent patients on RRT, the annual risk of death was 10.65% in 2008, 9.35% in 2009 and 8.86% in 2010. The overall mortality rate was 12.5 per 100 patient-years (95% confidence interval [95% CI], 12.1-13.0). The 5-year relative survival was 59% (95% CI, 57%-60%), and at 10 years relative survival was 41% (95% CI, 39%-43%); the estimated excess mortality rate was very high at the start of RRT (18 per 100 patient-years) but gradually decreased after the second year. On multivariate analysis, excess mortality was associated with age and primary renal diseases. Less than 10% of patients starting on PD shifted to HD in the first year of RRT, and a considerable proportion received a transplant, amounting to 6% in the first year, and thereafter increasing steadily: at the end of the fifth year, 34% of patients starting RRT on PD had received a transplant. HD patients behaved differently: any shift to PD was negligible, and the patients receiving a transplant amounted to only 2% in the first year and about 16% by the end of the fifth year. Cumulative mortality among HD patients was particularly high (already 18% at 1 year, and 70% at 10 years) by comparison with those on PD (8% at 1 year, 54% at 10 years). Although mortality on RRT is not particularly high in Veneto by comparison with countries other than Italy, this result is mainly due to an increasing number of patients receiving transplants, which makes them a favorably selected population. The mortality rate was high among those on HD, particularly in the first year. Our population on RRT is rather heterogeneous, and a description of the outcomes based only on the whole population may be misleading.

PERITONEAL EQUILIBRATION TEST REFERENCE VALUES USING A 3.86% GLUCOSE SOLUTION DURING THE FIRST YEAR OF PERITONEAL DIALYSIS: RESULTS OF A MULTICENTER STUDY OF A LARGE PATIENT POPULATION

Background: The original peritoneal equilibration test (PET) was used to classify peritoneal dialysis (PD) patients using a 2.27% glucose solution. It has since been suggested that a 3.86% glucose solution be used because this provides better information about ultrafiltration (UF) capacity and the sodium (Na) sieving of the peritoneal membrane. Objective: The aim of this study was to determine reference values for a PET using a 3.86% glucose solution (PET-3.86%). Methods: We evaluated the PET-3.86% in a large population of incident PD patients attending 27 Italian dialysis centers. Results: We evaluated the results of 758 PET-3.86% in 758 incident PD patients (1 test per patient). The mean duration of PD was 5 ± 3 months. The ratio of the concentrations of creatinine in dialysate/plasma (D/PCreat) was 0.73 ± 0.1 (median 0.74). The ratio between the concentrations of glucose at the end/beginning of the test (D/D0) was 0.25 ± 0.08 (median 0.24). Ultrafiltration uncorrected and corrected for bag overfill was respectively 776 ± 295 mL (median 781 mL) and 675 ± 308 mL (median 689 mL). Sodium sieving was 8.4 ± 3.8 mmol/L (median 8.0 mmol/L). Conclusion: The results of the study provide PET-3.86% reference values for the beginning of PD that can be used to classify PD patients into transport classes and monitor them over time.

Ionic conductivity of peritoneal dialysate: a new, easy and fast method of assessing peritoneal membrane function in patients undergoing peritoneal dialysis

BACKGROUND Peritoneal membrane function can be assessed using the peritoneal equilibration test (PET) and similar tests, but these are almost always complicated to use, require a considerable amount of working time and their results cannot always be easily interpreted. Ionic conductivity is a measure of the ability of an electrolyte solution to conduct electricity. We tested the hypothesis that the ionic conductivity of peritoneal dialysate can be used to evaluate peritoneal membrane function in peritoneal dialysis patients. METHODS We measured the ionic conductivity and classic biochemical parameters of peritoneal dialysate in 69 patients during a modified PET and compared their ability to evaluate peritoneal membrane function and to diagnose ultrafiltration failure (UFF). RESULTS Ionic conductivity was correlated well with classical parameters of peritoneal transport as glucose reabsorption of glucose (D/D0: r(2) = 0.62, P < 0.0001) and creatinine transport (D/PCreat: r(2) = 0.72, P < 0.0001). Twelve patients (17%) experienced UFF and, in them, the ionic conductivity area under the receiver-operating characteristic curve was 0.91 (95% confidence interval: 0.81-0.96) with sensitivity of 1.00 and specificity of 0.84 at a cut-off value of 12.75 mS/cm. CONCLUSIONS These findings indicate that the ionic conductivity of peritoneal dialysate can be used as a new screening tool to evaluate peritoneal membrane function.