Use of Renin-Angiotensin System Blockers Increases Serum Potassium in Anuric Hemodialysis Patients.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are increasingly used in uremic patients (pts). However, their effect on serum potassium (sK) concentrations in anuric pts on chronic hemodialysis treatment (HD) is controversial. The aim of the study was to evaluate sK before and after the start of ACEi/ARB therapy. METHODS: In the period 1/1/2015 - 31/12/2015, 112 out of 240 prevalent HD pts on thrice weekly HD treatment followed at our institution started the ACEi/ARB therapy. The mean age was 67 ± 14 years, 67/112 were men, dialysis vintage was 6-212 months. In the 3 months before (PRE; N° 36 HD sessions) and after (POST; N° 36 HD sessions) the start of ACEi/ARB therapy, the following variables were evaluated in pre dialysis after the long interdialysis interval: sK (mean of 12 determinations; mmol/L), maximum sK (maximum K value observed during observations; sKmax; mmol/L), serum sodium (sNa; mmol/L), pre dialysis systolic blood pressure (SBP; mm Hg) and diastolic blood pressure (DBP; mm Hg), body weight (BW; Kg), interdialytic weight gain (IWG; Kg), Kt/V, serum bicarbonate concentrations (sBic; mmol/L), protein catabolic rate (PCRn; g/KgBW/day). SBP, DBP, IWG are the mean of the 24 HD sessions. Out of 112 patients, 102 were on antihypertensive therapy. The duration of HD and blood and dialysate flow rates were kept constant. Data are expressed as mean ± SD. Student t test for paired and unpaired data for normally distributed variables, Mann-Whitney test for medians, χ2 test for categorical data were employed to compare groups. A significant difference was defined as p < 0.05. RESULTS: sK increased from 5.0 ± 0.4 mmol/L PRE to 5.7 ± 0.5 mmol/L POST (p < 0.0001). sKmax increased from 5.3 ± 0.5 mmol/L PRE to 6.2 ± 0.6 mmol/L POST (p < 0.0001). The percentage of pts with normal sK concentrations decreased from 82% PRE to 29% POST (p < 0.0001). Mild hyperkalemia increased from 18 to 52% (p < 0.001); in 31% of the patients, it was necessary to reduce the K dialysate concentration. None of the patients had severe hyperkalemia PRE, but 19% developed severe hyperkalemia POST (p < 0.0001) necessitating treatment withdrawal. Mean sK in these pts varied from 5.2 ± 0.3 mmol/L PRE to 6.5 ± 0.2 mmol/L at the moment of withdrawal (p < 0.0001) and sKmax from 5.5 ± mmol/L PRE to 6.9 ± 0.3 mmol/L (p< 0.0001). After withdrawal of ACEi/ARB, sK and sKmax concentrations decreased to basal levels within 1 month. There were no significant changes of BW, IWG, SBP, DBP, Na, Hb, Kt/V, sBic, and PCRn in both periods. CONCLUSIONS: ACEi/ARB therapy is associated with an increased risk of hyperkalemia in anuric hemodialysis patients. The proportion of patients with normal sK concentrations decreased from 82 to 29% and with mild hyperkalemia increased from 18 to 52%. Severe hyperkalemia necessitating the interruption of ACEi/ARB therapy developed in 19% of patients. This suggests great caution in the widest utilization of this class of drugs in HD patients.

Thiazide increases serum calcium in anuric patients: the role of parathyroid hormone.

We evaluated the effect of hydrochlorothiazide in a sample of anuric patients on hemodialysis and found an increase in serum calcium, which occurred only in those with parathyroid hormone >300 pg/ml. This finding highlights the extra-renal effect of this diuretic and a possible role of parathyroid hormone in the mechanism. PURPOSE: Thiazide diuretics are commonly used in patients with chronic kidney disease to treat hypertension. Their effects on calcium and bone metabolism are not well established, once calciuria may not fully explain levels of calcium and parathyroid hormone (PTH) in this population. A previous study has suggested that thiazides require the presence of PTH as a permissive condition for its renal action. In anuric patients, however, the role of PTH, if any, in the thiazide effect is unknown. METHODS: To assess thiazide extra renal effect on serum calcium and whether such an effect is reliant on PTH, hydrochlorothiazide (HCTZ) 100 mg was given orally once a day to a sample of 19 anuric patients on hemodialysis for 2 weeks. Laboratories' analyses were obtained in three phases: baseline, after diuretic use, and after a 2-week washout phase. RESULTS: We demonstrated that serum calcium (Ca) increased in ten patients (52.6%) after HCTZ use, returning to previous levels after the washout period. Out of the 19 patients, ten presented PTH ≥ 300 pg/ml, and Ca has increased in eight of them, whereas in the other nine patients with PTH < 300 pg/ml, serum Ca has increased only in two individuals (RR risk of increase Ca 3.9; p = 0.012). CONCLUSIONS: HCTZ was capable of increasing serum Ca in a sample of anuric patients on hemodialysis and seems this effect is highly dependent on PTH levels. Caution is required while interpreting this result, as the small sample size might implicate in a finding caused by chance.

The Role of Dialysis Membranes on Intradialytic Selenium Removal and on Selenium Status in Patients Receiving Renal Replacement Therapy.

BACKGROUND/AIMS: Dialysis membrane has been implicated in selenium (Se) deficiency in hemodialysis (HD). Intradialytic Se removal into dialysate through different membranes was investigated. METHODS: We studied 19 patients on standard HD with low-flux polysulfone membrane (group A), 10 patients on standard HD with ethylene vinyl alcohol membrane (group B), 12 patients on hemodiafiltration (HDF; group C) and 16 healthy subjects (control group D). Se was measured in blood before and after dialysis session and in effluent dialysate every hour during session. RESULTS: In all patients together, pre-dialysis serum Se levels were lower than those in control group, but, in a separate analysis, only in standard HD. In all patient groups, there was a net Se removal into dialysate but it was greater in HDF patients who, however, had similar pre-dialysis serum Se levels to those in healthy controls. CONCLUSION: An intradialytic Se loss was found with all 3 membrane types, but it is not the principal factor for Se depletion in HD.

Low Serum Bicarbonate Predicts Residual Renal Function Loss in Peritoneal Dialysis Patients.

Low residual renal function (RRF) and serum bicarbonate are associated with adverse outcomes in peritoneal dialysis (PD) patients. However, a relationship between the 2 has not yet been determined in these patients. Therefore, this study aimed to investigate whether low serum bicarbonate has a deteriorating effect on RRF in PD patients.This prospective observational study included a total of 405 incident patients who started PD between January 2000 and December 2005. We determined risk factors for complete loss of RRF using competing risk methods and evaluated the effects of time-averaged serum bicarbonate (TA-Bic) on the decline of RRF over the first 3 years of dialysis treatment using generalized linear mixed models.During the first 3 years of dialysis, 95 (23.5%) patients became anuric. The mean time until patients became anuric was 20.8 ±â€Š9.0 months. After adjusting for multiple potentially confounding covariates, an increase in TA-Bic level was associated with a significantly decreased risk of loss of RRF (hazard ratio per 1 mEq/L increase, 0.84; 0.75-0.93; P = 0.002), and in comparison to TA-Bic ≥ 24 mEq/L, TA-Bic < 24 mEq/L conferred a 2.62-fold higher risk of becoming anuric. Furthermore, the rate of RRF decline estimated by generalized linear mixed models was significantly greater in patients with TA-Bic < 24 mEq/L compared with those with TA-Bic ≥ 24 mEq/L (-0.16 vs -0.11 mL/min/mo/1.73 m, P < 0.001).In this study, a clear association was found between low serum bicarbonate and loss of RRF in PD patients. Nevertheless, whether correction of metabolic acidosis for this indication provides additional protection for preserving RRF in these patients is unknown. Future interventional studies should more appropriately address this question.

Ranking of factors determining potassium mass balance in bicarbonate haemodialysis.

BACKGROUND: One of the most important pathogenetic factors involved in the onset of intradialysis arrhytmias is the alteration in electrolyte concentration, particularly potassium (K(+)). METHODS: Two studies were performed: Study A was designed to investigate above all the isolated effect of the factor time t on intradialysis K(+) mass balance (K(+)MB): 11 stable prevalent Caucasian anuric patients underwent one standard (∼4 h) and one long-hour (∼8 h) bicarbonate haemodialysis (HD) session. The latter were pair-matched as far as the dialysate and blood volume processed (90 L) and volume of ultrafiltration are concerned. Study B was designed to identify and rank the other factors determining intradialysis K(+)MB: 63 stable prevalent Caucasian anuric patients underwent one 4-h standard bicarbonate HD session. Dialysate K(+) concentration was 2.0 mmol/L in both studies. Blood samples were obtained from the inlet blood tubing immediately before the onset of dialysis and at t60, t120, t180 min and at end of the 4- and 8-h sessions for the measurement of plasma K(+), blood bicarbonates and blood pH. Additional blood samples were obtained at t360 min for the 8 h sessions. Direct dialysate quantification was utilized for K(+)MBs. Direct potentiometry with an ion-selective electrode was used for K(+) measurements. RESULTS: Study A: mean K(+)MBs were significantly higher in the 8-h sessions (4 h: -88.4 ± 23.2 SD mmol versus 8 h: -101.9 ± 32.2 mmol; P = 0.02). Bivariate linear regression analyses showed that only mean plasma K(+), area under the curve (AUC) of the hourly inlet dialyser diffusion concentration gradient of K(+) (hcgAUCK(+)) and AUC of blood bicarbonates and mean blood bicarbonates were significantly related to K(+)MB in both 4- and 8-h sessions. A multiple linear regression output with K(+)MB as dependent variable showed that only mean plasma K(+), hcgAUCK(+) and duration of HD sessions per se remained statistically significant. Study B: mean K(+)MBs were -86.7 ± 22.6 mmol. Bivariate linear regression analyses showed that only mean plasma K(+), hcgAUCK(+) and mean blood bicarbonates were significantly related to K(+)MB. Again, only mean plasma K(+) and hcgAUCK(+) predicted K(+)MB at the multiple linear regression analysis. CONCLUSIONS: Our studies enabled to establish the ranking of factors determining intradialysis K(+)MB: plasma K(+) → dialysate K(+) gradient is the main determinant; acid-base balance plays a much less important role. The duration of HD session per se is an independent determinant of K(+)MB.

A prospective assessment of renal oxygenation in children undergoing laparoscopy using near-infrared spectroscopy.

BACKGROUND: This study was designed to determine whether a decrease in renal oxygenation occurs during CO2 pneumoperitoneum in children with normal renal function undergoing laparoscopy. METHODS: Near infrared spectroscopy (NIRS) probes were applied to both the lateral flank (T10-L2) and lateral cerebral area of all patients with normal renal function undergoing a laparoscopic procedure. Information was recorded in 5-s intervals for 15-min before, during, and for 15-min after pneumoperitoneum insufflation and desufflation. Simultaneously, additional hemodynamic parameters (arterial saturation, mean arterial pressure, end tidal CO2, and urine output) were recorded every 5-min. Pneumoperitoneum pressures used were: 0-1 month old, <6 mmHg; 2-12 months old, <8 mmHg; 1-2 years old, <10 mmHg, and 2-8 years old, <12 mmHg. The lowest possible pressure was used to obtain adequate vision. RESULTS: Twenty-nine patients were enrolled in the study. Renal regional oxygen saturation (rSO2) did not decrease significantly between baseline (preinsufflation), insufflation, and desufflation of the pneumoperitoneum (p = 0.343). Meta-analysis of this data demonstrated a pooled weighted difference of -1.4 (-3.5 to 0.54), confirming no significant change. A significant increase in cerebral rSO2 occurred during the insufflation period of the CO2 pneumoperitoneum (p = 0.001). Heart rate (F = 11.05; p < 0.001) and mean arterial pressure (MAP) (F = 19.2; p < 0.001) also increased significantly during the laparoscopy. No significant correlation was identified between fluid input and urine output during the laparoscopy (r = 0.012; p = 0.953). CONCLUSIONS: Renal hypoxia does not occur during laparoscopic surgery in children if the minimum age-appropriate intra-abdominal pressures are used. Alternative causes must account for the oliguria and anuria demonstrated in children undergoing laparoscopy.

Peritoneal phosphate removal varies by peritoneal dialysis regimen: an underestimated parameter of phosphate control.

BACKGROUND: The optimization of phosphate (P) removal by peritoneal dialysis (PD) is often underestimated. Our objective was to investigate peritoneal P clearance and its relationship with standard adequacy targets, hyperphosphatemia and automated PD (APD) parameters. METHODS: Dialysis dose, P clearances (24-hour urine and effluent samples), estimated percentage of diffusive P removal and peritoneal transport rate (PET) were evaluated in 77 adult prevalent PD patients. RESULTS: Total P removal strongly correlated with residual renal function parameters, dissociated from peritoneal Kt/V urea (r=-0.36; p=0.02) and creatinine clearance (r=-0.32; p<0.0001). A correlation of P clearance with net ultrafiltration was not found. Among the variables studied, only renal and peritoneal P clearances were significantly lower in hyperphosphatemic patients. In APD, peritoneal phosphate clearance was positively correlated with 4-hour dialysate to plasma creatinine ratio (r=0.46; p=0.039). Slow transporters had higher peritoneal P clearances under continuous ambulatory PD (CAPD) regimens. Hyperphosphatemia was significantly associated with a lower number of APD cycles and shorter nightly therapy time, with insufficient dwell time individualization. CONCLUSIONS: P peritoneal clearance is a modifiable parameter of P control in PD regimens and an additional adequacy target. Prescription skills are recommended in APD patients, particularly in anurics, to take into account peritoneal transport rate.

Sodium setpoint and gradient in bicarbonate hemodialysis.

BACKGROUND: The demonstration of an individual osmolar setpoint in hemodialysis (HD) is crucial to individualize dialysate sodium concentrations. Furthermore, the diffusive gradient between plasma and dialysate sodium is important in the "fine tuning" of the intradialytic sodium mass balance (MB). METHODS: The design of this study included part A: a retrospective analysis of predialysis plasma sodium concentrations extracted from a 6-year database in our HD population (147 prevalent white anuric patients); and part B: study of intradialytic sodium kinetics in 48 patients undergoing one 4-hour bicarbonate HD session. Direct potentiometry with an ion-selective electrode was used for sodium measurements. RESULTS: Study part A: the mean number of plasma sodium measurements per patient was 16.06 ± 14.03 over a mean follow-up of 3.55 ± 1.76 years. The mean of the averaged plasma sodium concentrations was 136.7 ± 2.1 mmol/L, with a low mean intraindividual coefficient of variation (1.39 ± 0.4). Study part B: mean predialysis and postdialysis plasma sodium concentrations were 135.8 ± 0.9 and 138.0 ± 0.9 mmol/L (p<0.001). Mean inlet dialyzer sodium concentration was 138.7 ± 1.1 mmol/L; the hourly diffusion concentration gradients showed a statistically significant transfer from dialysate to plasma (Wilks ? <0.0001). A statistically significant relationship was found between sodium MB and diffusion gradient (p<0.02), and between sodium MB and ultrafiltration volume (p<0.01). CONCLUSIONS: A relatively "fixed" and individual osmolar setpoint in HD patients was shown for the first time in a long-term follow-up. A dialysate sodium concentration of 140 mmol/L determined a dialysate to plasma sodium gradient.

Effects of different dialysate calcium concentrations on intradialysis hemodynamic stability.

BACKGROUND: The interplay of correct solute mass balances, such as those of sodium (Na+), potassium (K+) and total calcium (tCa) (Na+MB, K+MB and tCaMB, respectively) with adequate ultrafiltration volumes (VUF) is crucial to achieving hemodynamic stability during hemodialysis (HD). METHODS: Twenty-two stable anuric uremic patients underwent three 4-hour bicarbonate HD sessions, each with a different dialysate tCa concentration (1.25, 1.375 and 1.50 mmol/L). The GENIUS dialysis system (Fresenius Medical Care, Germany) was used. Volumes of blood and dialysate processed, VUF and dialysate Na+ and K+ concentrations were prescribed to be the same. Hourly measurements of plasma water ionized Ca (Ca++), Na+ and K+ were made, and their trends analyzed. tCaMBs, Na+MBs and K+MBs were determined. Systolic (SBP), diastolic (DBP) blood pressure, mean arterial pressure (MAP) and heart rate (HR) trends during dialysis were analyzed. RESULTS: Mean hourly plasma water Ca++ concentrations were statistically significantly higher with a dialysate tCa concentration of 1.50 mmol/L. Mean tCaMBs were positive (diffusion gradient from the dialysate to the patient), increasing with increasing dialysate tCa concentrations (+75 ± 122 mg, +182 ± 125 mg, +293 ± 228 mg, respectively). Their difference was statistically significant (p<0.0005). Mean Na+MBs and K+MBs were not statistically significantly different. SBP, DBP, MAP and HR were not statistically significantly different among the 3 treatments. CONCLUSIONS: These highly controlled experiments showed that hemodynamic stability does not appear to be statistically significantly influenced by any specific dialysate tCa concentration in this peculiar subset of patients.

Investigating the mechanism for maintaining eucalcemia despite immobility and anuria in the hibernating American black bear (Ursus americanus).

Ursine hibernation uniquely combines prolonged skeletal unloading, anuria, pregnancy, lactation, protein recycling, and lipolysis. This study presents a radiographic and biochemical picture of bone metabolism in free-ranging, female American black bears (Ursus americanus) that were active (spring bears and autumn bears) or hibernating (hibernating bears). Hibernating bears included lactating and non-lactating individuals. We measured serum calcium, albumin, inorganic phosphate, creatinine, bone specific alkaline phosphatase (BSALP), CTX, parathyroid hormone, insulin-like growth factor-I (IGF-l), leptin, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and sclerostin from 35 to 50 tranquilized hibernating bears and 14 to 35 tranquilized spring bears. We compared metacarpal cortical indices (MCI), measured by digital X-ray radiogrammetry, from 60 hunter-killed autumn bears and 79 tranquilized, hibernating bears. MCI was greater in autumn than winter in younger bears, but showed no seasonal difference in older bears. During hibernation eucalcemia was maintained, BSALP was suppressed, and CTX was in the range expected for anuria. During hibernation 1,25(OH)(2)D was produced despite anuria. 1,25(OH)(2)D and IGF-I were less in hibernating than spring bears. In a quarter of hibernating bears, sclerostin was elevated. Leptin was greater in hibernating than spring bears. In hibernating bears, leptin correlated positively with BSALP in non-lactating bears and with CTX in lactating bears. Taken together the biochemical and radiographic findings indicate that during hibernation, bone turnover was persistent, balanced, and suppressed; bone resorption was lower than expected for an unloaded skeleton; and there was no unloading-induced bone loss. The skeleton appears to perceive that it was loaded when it was actually unloaded during hibernation. However, at the level of sclerostin, the skeleton recognized that it was unloaded. During hibernation leptin appeared anabolic in non-lactating bears and catabolic in lactating bears. We hypothesize that ursine hibernation may represent a natural model in which suppression of the sympathetic nervous system prevents unloading-induced bone loss by influencing leptin's skeletal effects and preventing transmission of loading information.

Variability of pulse wave velocity and mortality in chronic hemodialysis patients.

We have already demonstrated that in chronic hemodialysis (HD) patients, the cyclic variations in both hydration status and blood pressure are responsible for changes in pulse wave velocity (PWV). The aim of this study is to verify whether the cyclic variation of PWV influences mortality in dialysis patients. We studied 167 oligoanuric (urinary output <500 mL/day) patients on chronic standard bicarbonate HD for at least 6 months. They performed 3 HD sessions of 4 hours per week. Patients were classified into 3 groups: normal PWV before and after dialysis (LL); high PWV before and normal PWV after dialysis (HL); and high PWV before and after dialysis (HH). The carotid-femoral PWV was measured with an automated system using the foot-to-foot method. Analysis of variance was used to compare the different groups. The outcome event studied was all-cause mortality and cardiovascular mortality. The PWV values observed were LL in 44 patients (26.3%); HL in 53 patients (31.8%); and HH in 70 patients (41.9%). The 3 groups of patients are homogenous for sex, age, and blood pressure. The HH group had a higher prevalence of (P<0.001) ASCVD. It is interesting that the distribution of patients in the 3 groups is correlated with the basal value of PWV. In fact, when the basal measure of PWV is elevated, there is a higher probability that an HD session cannot reduce PWV (<12 ms). A total of 53 patients (31.7%) died during the follow-up of 2 years: 5 patients in the LL group (11.4%); 16 in the HL group (30.2%); and 32 in the HH group (50.7%) (LL vs. HL, P=0.047; LL vs. HH, P<0.00001; HL vs. HH, P=0.034). We evidence for the first time that different behaviors of PWV in dialysis subjects determine differences in mortality.

Role of residual renal function in phosphate control and anemia management in chronic hemodialysis patients.

BACKGROUND AND OBJECTIVES: There is increasing awareness that residual renal function (RRF) has beneficial effects in hemodialysis (HD) patients. The aim of this study was to investigate the role of RRF, expressed as GFR, in phosphate and anemia management in chronic HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Baseline data of 552 consecutive patients from the Convective Transport Study (CONTRAST) were analyzed. Patients with a urinary output≥100 ml/24 h (n=295) were categorized in tertiles on the basis of degree of GFR and compared with anuric patients (i.e., urinary output<100 ml/24 h, n=274). Relations between GFR and serum phosphate and erythropoiesis-stimulating agent (ESA) index (weekly ESA dose per kg body weight divided by hematocrit) were analyzed with multivariable regression models. RESULTS: Phosphate levels were between 3.5 and 5.5 mg/dl in 68% of patients in the upper tertile (GFR>4.13 ml/min per 1.73 m2), as compared with 46% in anuric patients despite lower prescription of phosphate-binding agents. Mean hemoglobin levels were 11.9±1.2 g/dl with no differences between the GFR categories. The ESA index was 31% lower in patients in the upper tertile as compared with anuric patients. After adjustments for patient characteristics, patients in the upper tertile had significantly lower serum phosphate levels and ESA index as compared with anuric patients. CONCLUSIONS: This study suggests a strong relation between RRF and improved phosphate and anemia control in HD patients. Efforts to preserve RRF in HD patients could improve outcomes and should be encouraged.

Peritoneal membrane phosphate transport status: a cornerstone in phosphate handling in peritoneal dialysis.

BACKGROUND AND OBJECTIVES: Phosphate control impacts dialysis outcomes. Our aim was to define peritoneal phosphate transport in peritoneal dialysis (PD) and to explore its association with hyperphosphatemia, phosphate clearance (PPhCl), and PD modality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two hundred sixty-four patients (61% on continuous ambulatory PD [CAPD]) were evaluated at month 12. PPhCl was calculated from 24-hour peritoneal effluent. Phosphate (Ph) and creatinine (Cr) dialysate/plasma (D/P) were calculated at a 4-hour 3.86% peritoneal equilibration test. RESULTS: D/PPh correlated with D/PCr. PPhCl correlated better with D/PPh than with D/PCr. Prevalence of hyperphosphatemia (>5.5 mg/dl) was 30%. In a multiple regression analysis, only residual renal function was independently, negatively associated with hyperphosphatemia; in anuric patients, only D/PPh was an independent factor predicting hyperphosphatemia. D/PPh was 0.57 ± 0.10, and according to this, 16% of the patients were fast, 31% were fast-average, 35% were slow-average, and 17% were slow transporters. PPhCl was 37.5 ± 11.7 L/wk; it was lower in the slow transporter group (31 ± 14 L/wk). Among fast and fast-average transporters, PPhCl was comparable in both PD modalities. In comparison to automated PD, CAPD was associated with increased PPhCl among slow-average (36 ± 8 versus 32 ± 7 L/wk) and slow transporters (34 ± 15 versus 24 ± 9 L/wk). CONCLUSIONS: In hyperphosphatemic, particularly anuric, patients, optimal PD modality should consider peritoneal phosphate transport characteristics. Increasing dwell times and transfer to CAPD are effective strategies to improve phosphate handling in patients with inadequate phosphate control on automated PD.

Vancomycin pharmacokinetics and pharmacodynamics during short daily hemodialysis.

BACKGROUND AND OBJECTIVES: Short daily hemodialysis (SDHD) is an alternative to thrice-weekly HD because of its putative physiologic benefits. The purpose of this study was to investigate the effect of SDHD on the pharmacokinetics and pharmacodynamics of vancomycin. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Six noninfected adults who had anuria and were treated with SDHD were studied and received four dialysis sessions over 4 days. After completion of the first SDHD, each patient received vancomycin 15 mg/kg by intravenous infusion. Blood samples were collected over the ensuing 3 days during each subsequent inter- and intradialytic period. Pharmacokinetic parameters were determined. Serum concentration-time profiles were simulated for four vancomycin regimens with maintenance doses administered after every other SDHD. Area under the serum-concentration time curve (AUC) from 0 to 48 hours, 48 to 96 hours, and 96 to 144 hours were calculated, and Monte Carlo simulations were performed to determine the probability of target attainment at an AUC/minimum inhibitory concentration (MIC) ratio ≥800 for each 48-hour AUC at MICs ranging from 0.5 to 2.0 µg/ml. RESULTS: Median (range) systemic clearance was 7.2 ml/min (5.3 to 10.0 ml/min), and dialytic clearance was 104 ml/min (94 to 106 ml/min). The steady-state volume of distribution was 55.4 L (34.8 to 77.2 L). At MICs ≤1 µg/ml, probability of target attainment was >90% for each 48-hour AUC when vancomycin was administered as a 20-mg/kg loading dose followed by 10 mg/kg after every other SDHD. CONCLUSIONS: Vancomycin pharmacokinetic parameters in SDHD are consistent with data from thrice-weekly HD. A loading dose of 20 mg/kg followed by 10 mg/kg after every other SDHD provides adequate exposure for pathogens with MICs ≤1 µg/ml.

Serum cystatin C: a surrogate marker for the characteristics of peritoneal membrane in dialysis patients.

To evaluate whether cystatin C levels can be a surrogate marker of creatinine clearance and reflect the characteristics of peritoneal membrane in dialysis patients, we performed peritoneal equilibration tests (PET) in 18 anuric adult chronic peritoneal dialysis (PD) patients with a mean age of 39.7 +/- 20 years. All the samples were analyzed for urea, creatinine, and cystatin C. Peritoneal transport, mass transfer, and peritoneal clearance of cystatin C were calculated. Correlation and regression analysis was done using cystatin C as a dependent variable and age, sex, height, weight, body surface area, and creatinine as independent variables. Cystatin C demonstrated a significant time dependent increase of dialysate concentration and decline in the serum concentrations during PET, and a strong correlation between serum creatinine and serum cystatin C concentrations(r: 0.62, p= 0.008). The trans-peritoneal clearance (mL/min/1.73 m 2 ) of cystatin C was related to its serum concentration and was similar to creatinine in its pattern but of smaller magnitude. Peritoneal mass transfer (mg/4 hr per 1.73 m 2 ) for cystatin C serum creatinine was 1.68 +/- 0.67 and 73.3 +/- 29.8, respectively. The dialysis/plasma D/P cystatin C concentration was > or = 0.1 at 4 hrs of PET denoted high peritoneal transport, while the values of < 0.1 denoted low transport type. We conclude that cystatin C follows the same pattern of peritoneal exchange as creatinine but the magnitude of transfer is many folds lower than creatinine. At present clinical utility of cystatin C in the evaluation of solute clearance is probably limited due to the minute amounts transferred across the membrane and the high renal clearance in the presence of residual renal function.

A probable case of gabapentin-related reversible hearing loss in a patient with acute renal failure.

BACKGROUND: As described in the literature, gabapentin toxicity in patients with impaired renal function can manifest as coma, myoclonus, tremulousness, or altered mental status. Gabapentin is an antiepileptic agent indicated for use as an adjunct therapy in partial seizures and postherpetic neuralgia but is also prescribed for the treatment of diabetic peripheral neuropathy. CASE SUMMARY: A 46-year-old white woman (height, 167 cm; weight, 177 kg; body mass index, 62.8 kg/m2) with a 6-year history of diabetes mellitus and previously normal renal function, presented to the emergency department of Wake Forest University Baptist Medical Center with anuria (a serum creatinine level of 7.4 mg/dL), hearing loss, myoclonus, and confusion with hallucinations lasting for 3 days. Her blood pressure was 110/74 mm Hg. The patient's preadmit medication list included: lisinopril (40 mg QD), hydrochlorothiazide (25 mg QD), and furosemide (80 mg QD) for hypertension; atorvastatin (10 mg QD) for hyperlipidemia; omeprazole (20 mg QD) for gastroesophageal reflux disease; salmeterol/fluticasone inhaler (100/50 microg; 1 puff BID) and albuterol metered-dose inhaler (90 microg as needed) for asthma; metformin (500 mg BID) and insulin lispro per sliding scale for type 2 diabetes mellitus; oxycodone controlled release (60 mg TID) for chronic osteoarthritis and low back pain; alprazolam (0.5 mg every 8 hours as needed) for generalized anxiety disorder; venlafaxine (150 mg BID) for depression; and gabapentin (300 mg TID) for diabetic peripheral neuropathy. The patient's symptoms (hearing loss, myoclonus, and confusion) improved after 1 session of hemodialysis (approximately 10 hours following admission) and had resolved at the time of discharge (4 days later). On admission, the gabapentin concentration was 17.6 microg/mL, and following hemodialysis, the gabapentin concentration was undetectable (by discharge/day 4). The timing of the patient's last dose of gabapentin is unknown. Normal doses for the treatment of diabetic peripheral neuropathy range from 900 to 3600 mg/d divided 3 times daily. CONCLUSIONS: We report a patient with acute renal failure who developed hearing loss, myoclonus, and confusion with hallucinations in the presence of elevated gabapentin concentrations. Due to rapid improvement after hemodialysis and discontinuation of gabapentin, we believe that these symptoms were probably due to gabapentin toxicity.

Prolonged renal failure secondary to antithymocyte globulin treatment in severe aplastic anemia.

OBJECTIVE: To report a case of acute renal failure in a patient with severe aplastic anemia after administration of antithymocyte globulin (ATG). CASE SUMMARY: A 41-year-old man diagnosed with severe aplastic anemia was treated with ATG and cyclosporine. After one dose of ATG (3012 mg, 40 mg/kg), the patient developed anuric acute renal failure, with serum creatinine 3.4 mg/dL (1.2 mg/dL at baseline) and blood urea nitrogen (BUN) 29 mg/dL (13 mg/dL at baseline), which required intermittent hemodialysis. Renal failure resolved with cessation of the drug, serum creatinine and BUN returned to baseline levels, and the patient no longer required hemodialysis. DISCUSSION: ATG is a purified and concentrated gamma globulin, primarily a monomeric immunoglobulin G from hyperimmune serum of horses. It is widely used to treat severe aplastic anemia and to manage acute transplant rejection. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment using the Naranjo probability scale suggested that ATG was the probable cause of the acute renal failure. Primary glomerular disease was not excluded, as a renal biopsy was not performed. CONCLUSIONS: The association between renal injury and administration of ATG remains unclear; therefore, we recommend that renal function be assessed and carefully monitored prior to and after administration of ATG.