Residual Renal Phosphate Clearance in Patients Receiving Hemodialysis or Hemodiafiltration.

OBJECTIVES: Substantial levels of residual renal clearance and urine output may occur in patients treated with hemodialysis or hemodiafiltration. However, the relationships among residual renal urea, creatinine, and phosphate clearances, respectively, and between clearances and urine volume have not been well described. METHODS: We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of >100 mL/day, in whom at least 2 residual renal clearances were obtained over a 6-month observation period. Urine was collected for 24 hours prior to the midweek treatment session and concentrations of urea, creatinine, and phosphate were measured. RESULTS: Thirty-eight patients (24 men, 14 women) with a mean age of 70.4 ± 12.4 (SD) years were included in this analysis. All patients were dialyzed 3 times per week with mean treatment duration of 243 ± 7.89 minutes. Twenty patients were undergoing hemodiafiltration and 18 patients high-flux hemodialysis. In total, 102 dialysis sessions, of which 52 were hemodiafiltration, and urine collections were analyzed. Mean urine volume was 457 ± 254 mL per 24 hours. Residual renal clearance rates of urea (Kr Urea), creatinine (Kr Cr), and phosphate (Kr Phos) were 1.60 ± 0.979, 4.69 ± 3.79, and 1.98 ± 1.36 mL/minute, respectively. Mean ratios of Kr Cr/Kr Urea, Kr Phos/Kr Urea, and Kr Phos/Kr Cr were 2.83 ± 1.21, 1.23 ± 0.387, and 0.477 ± 0.185, respectively. There was a modest correlation between Kr Phos and daily urine volume (r = 0.605, P = .001). CONCLUSIONS: In maintenance hemodialysis and hemodiafiltration patients, residual renal phosphate clearance is approximately 23% higher than residual renal urea clearance. Urine volume is a modestly accurate surrogate for estimating residual renal phosphate clearance, but only when urine volume is <300 mL/day.

Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study.

RATIONALE & OBJECTIVE: Thrice-weekly hemodialysis (HD) is the most common treatment modality for kidney failure in the United States. We conducted a pilot study to assess the feasibility and safety of incremental-start HD in patients beginning maintenance HD. STUDY DESIGN: Pilot study. SETTING & PARTICIPANTS: Adults with estimated glomerular filtration rate (eGFR) ≥5 mL/min/1.73 m2 and urine volume ≥500 mL/d beginning maintenance HD at 14 outpatient dialysis units. EXPOSURE: Randomized allocation (1:1 ratio) to twice-weekly HD and adjuvant pharmacologic therapy for 6 weeks followed by thrice-weekly HD (incremental HD group) or thrice-weekly HD (conventional HD group). OUTCOME: The primary outcome was feasibility. Secondary outcomes included changes in urine volume and solute clearance. RESULTS: Of 77 patients invited to participate, 51 consented to do so, representing 66% of eligible patients. We randomized 23 patients to the incremental HD group and 25 patients to the conventional HD group. Protocol-based loop diuretics, sodium bicarbonate, and patiromer were prescribed to 100%, 39%, and 17% of patients on twice-weekly HD, respectively. At a mean follow-up of 281.9 days, participant adherence was 96% to the HD schedule (22 of 23 and 24 of 25 in the incremental and conventional groups, respectively) and 100% in both groups to serial timed urine collection. The incidence rate ratio for all-cause hospitalization was 0.31 (95% CI, 0.08-1.17); and 7 deaths were recorded (1 in the incremental and 6 in the conventional group). At week 24, the incremental HD group had lower declines in urine volume (a difference of 51.0 [95% CI, -0.7 to 102.8] percentage points) and in the averaged urea and creatinine clearances (a difference of 57.9 [95% CI, -22.6 to 138.4] percentage points). LIMITATIONS: Small sample size, time-limited twice-weekly HD. CONCLUSIONS: It is feasible to enroll patients beginning maintenance HD into a randomized study of incremental-start HD with adjuvant pharmacotherapy who adhere to the study protocol during follow-up. Larger multicenter clinical trials are indicated to determine the efficacy and safety of incremental HD with longer twice-weekly HD periods. FUNDING: Funding was provided by Vifor Inc. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, identifier NCT03740048.

Association of serum potassium with decline in residual kidney function in incident hemodialysis patients.

BACKGROUND: Hyperkalemia is associated with kidney function decline in patients with non-dialysis dependent chronic kidney disease, but this relationship is unclear for residual kidney function (RKF) among hemodialysis (HD) patients. METHODS: We conducted a retrospective cohort study of 6655 patients, who started HD January 2007 and December 2011 and who had data on renal urea clearance (KRU). Serum potassium levels were stratified into four groups (i.e. ≤4.0, >4.0 to ≤4.5, >4.5 to ≤5.0 and >5.0 mEq/L) and 1-year KRU slope for each group was estimated by a linear mixed-effects model. RESULTS: Higher serum potassium was associated with a greater decline in KRU, and the greatest decrease in KRU (-0.20, 95% confidence interval -0.50 to -0.06) was observed for baseline potassium >5.0 mEq/L in the fully adjusted model. Mediation analysis showed that KRU slope mediated 1.78% of the association between serum potassium and mortality. CONCLUSIONS: Hyperkalemia is associated with a decline in RKF amongst incident HD patients. These findings may have important clinical implications in the management of hyperkalemia in advanced CKD if confirmed in additional clinical trials.

Validation of a Protocol for Continuous Hemodiafiltration with Regional Citrate Anticoagulation with Omni®.

INTRODUCTION: Omni® (B Braun, Melsungen, Germany) is able to run continuous renal replacement therapy (CRRT) in continuous veno-venous hemofiltration (CVVH), hemodialysis (CVVHD), and hemodiafiltration (CVVHDF) modes. However, to date, there is no validated protocol to guide the use of Omni® in CVVHDF mode with regional citrate anticoagulation (RCA). METHODS: We designed a protocol for CVVHDF-RCA tailored for Omni®. This protocol was tested in patients included in an observational study conducted in our center between January and March 2021. For all study patients, we collected baseline characteristics, laboratory results, CRRT circuit lifespan as well as plasma and effluent samples at 12, 24, 48, and 72 h of CRRT circuit initiation. At each study time point, we computed urea, creatinine, and ß2-microglobulin clearance as well as effluent/blood ratios. Data from circuits in CVVHDF-RCA mode are compared with those in standard therapy (CVVHD-RCA) with the same device. RESULTS: We analyzed ten circuits (5 patients) in CVVHDF-RCA mode and 32 (13 patients) in CVVHD-RCA mode. No adverse events related to the therapy were observed. In CVVHDF-RCA mode, median circuit running time was 68 (IQR 8.1) hours versus 46 (IQR 9.0) in CVVHD mode, p = 0.053. Therapy adaptations (dialysate rate and/or blood flow) were required in one (10%) circuit (15.6% in CVVHD mode, p = 0.56). Compared to CVVHD, CVVHDF was able to achieve similar clearance and effluent/blood ratio for urea, creatinine, and ß2-microglobulin across the entire duration of circuit lifetime. CONCLUSION: The proposed protocol for CVVHDF-RCA for Omni® was associated with similar circuit lifetime, number of required adaptations and clearances to standard CVVHD-RCA. It appears to be safe and feasible.

Routine Kt/V and Normalized Protein Nitrogen Appearance Rate Determined From Conductivity Access Clearance With Infrequent Postdialysis Serum Urea Nitrogen Measurements.

RATIONALE & OBJECTIVES: Conventional monitoring of hemodialysis dose is implemented using urea kinetic modeling based on single-pool Kt/V, which requires both pre- and postdialysis serum urea nitrogen (SUN) measurements. We compared this conventional approach to one in which Kt/V is calculated using conductivity clearance, thereby reducing the need for regular postdialysis SUN measurements. STUDY DESIGN: Comparative study of 2 diagnostic tests. SETTING & PARTICIPANTS: Prevalent patients receiving maintenance hemodialysis for at least 2 years for whom both urea reduction ratio (URR) and average conductivity clearance (Kecn) were measured. TESTS COMPARED: During the initial 8 months (baseline interval), average Kecn and URR were used to calculate a median patient-specific, modeled, calibration solute distribution volume (Vcal). During months 9 to 16 (period 1) and 17 to 24 (period 2), Kt/V was conventionally computed using URR and also by a new method using Vcal and Kecn without postdialysis SUN values. We examined the percentage error between these 2 methods of calculating Kt/V. OUTCOMES: Concordance between the 2 methods of calculating Kt/V. RESULTS: Among 1,093 patients, mean individual-level median single-pool Kt/V values derived using the conventional method during the baseline interval, period 1, and period 2 were 1.62±0.24 (SD), 1.66±0.24, and 1.67±0.24, respectively. During periods 1 and 2, patient-level median Kt/V values derived using Kecn were 1.64±0.24 and 1.65±0.24, respectively. Percent differences between patient-level median values of Kt/V (conductivity minus conventional URR methods) were-0.63%±7.7% and-0.75%±8.4% for periods 1 and 2. Normalized protein nitrogen appearance were comparable between the 2 methods. LIMITATIONS: Data were collected over 2 years. Study was limited to in-center hemodialysis patients dialyzed 3 times per week. Dialysis session length was not adjusted for treatment interruptions. CONCLUSIONS: A new method of calculating Kt/V based on Kecn that requires fewer postdialysis SUN measurements provided diagnostic data comparable to those from conventional use of URR and has the potential to avoid errors related to postdialysis blood sampling and measurement.

End-Stage Kidney Patients Require Hemodialysis Therapy Full Start.

Recently the concept that prescription of chronic hemodialysis (HD) start should be tailored based on residual renal function (RRF) and urine output (UO) has been revived from the past and called infrequent or incremental dialysis. It mainly consists in prescribing 1 or 2 HD sessions per week instead of what has become the standard thrice-weekly HD. It is both surprising and fascinating that almost 60 years after the first end-stage kidney disease patient was treated by Scribner et al. [Trans Am Soc Artif Intern Organs 1960; 6: 114-122], the nephrology community still questions the best way to start HD therapy. This comforting process is the result of pieces of evidence accumulated with time such as that RRF is associated with better outcomes that starting HD therapy favors the loss of RRF and/or UO and also results in a high rate of deaths in the first weeks of HD therapy. Through this review, we support the idea that when the decision to start HD therapy is made, ideally with the full collaboration of the patient, it is necessary to be efficient to alleviate uremic symptoms, to correct the fluid overload and to allow a full recovery from the uremic state associated with the late stages of non-dialysis chronic kidney disease.

Treatment of Gabapentin Toxicity With Peritoneal Dialysis: Assessment of Gabapentin Clearance.

Gabapentin is almost exclusively cleared by the kidney and thus presents challenges in patients with kidney failure. Gabapentin is known to be effectively cleared by hemodialysis, but the efficiency of clearance by peritoneal dialysis (PD) has not been previously described. We report a case of gabapentin toxicity in a patient on long-term PD who was treated with continuous automated cycling PD. We find that continuous PD provides significant clearance of gabapentin. With 2-L exchanges every 2 hours, we document an apparent elimination half-life of 41.33 hours, which is substantially shorter than the reported elimination half-life of 132 hours in the absence of kidney function. Further, our patient's symptoms of gabapentin toxicity gradually improved and had fully resolved after about 36 hours of dialysis. Gabapentin clearance by PD was estimated at 94% of urea clearance. We conclude that intensive PD provides gabapentin clearance that approximates that of urea and is an effective but slow method to treat gabapentin overdose and toxicity.

The variable target model: a paradigm shift in the incremental haemodialysis prescription.

Background: The recent interest in incremental haemodialysis (HD) is hindered by the current prescription based on a fixed target model (FTM) for the total (dialytic + renal) equivalent continuous clearance (ECC). The latter is expressed either as standard Kt/V (stdKt/V), i.e. the pre-dialysis averaged concentration of urea-based ECC, or EKRc, i.e. the time averaged concentration-based ECC, corrected for volume (V) = 40 L. Accordingly, there are two different targets: stdKt/V = 2.3 volumes per week (v/wk) and EKRc = 13 mL/min/40 L. However, fixing the total ECC necessarily implies perfect equivalence of its components-the residual renal urea clearance (Kru) and dialysis clearance (Kd). This assumption is wrong because Kru has much greater clinical weight than Kd. Here we propose that the ECC target varies as an inverse function of Kru, from a maximum value in anuria to a minimum value at Kru levels not yet requiring dialysis. The aim of the present study was to compare the current FTM with the proposed variable target model (VTM). Methods: The double pool urea kinetic model was used to model dialysis sessions for 360 virtual patients and establish equations predicting the ECC as a function of Kd, Kru and the number of sessions per week. An end-dialysis urea distribution V of 35 L (corresponding to a body surface area of 1.73 m 2 ) was used, so that the current EKRc target of 13 mL/min/40 L could be recalculated at an EKRc 35 value of 12 mL/min/35 L equal to 12 mL/min/1.73 m 2 . The latter also coincides with the maximum value of the EKRc 35 variable target in anuria. The minimum target value of EKRc 35 was assumed to coincide with Kru corrected for V = 35 L (i.e. Krc 35 = 6 mL/min/1.73 m 2 ). The corresponding target for stdKt/V was assumed to vary from 2.3 v/wk at Krc 35 = 0 to 1.7 v/wk at Krc 35 = 6 mL/min/1.73 m 2 . On this basis, the variable target values can be obtained from the following linear equations: target EKRc 35 = 12 - Krc 35 ; target stdKt/V = 2.3 - 0.1 × Krc 35 . Two versions of stdKt/V were considered: the classic version (stdKt/V Gotch ) with Kru at 70%, and the current version (stdKt/V Daug ) with Kru at 100%. Results: The VTM with stdKt/V Gotch produces results very close to those using the FTM with stdKt/V Daug . Once-weekly HD is virtually not allowed by the FTM. In contrast, the VTM allows dialysis to start at Krc 35 ∼5 mL/min/1.73 m 2 on a once-weekly HD schedule, at least in relatively healthy patients; this schedule can be maintained until Krc 35 falls below 4 mL/min/1.73 m 2 , at which point the schedule should be changed to a twice-weekly HD schedule, that, in turn, could be maintained until Krc 35 falls below 2 mL/min/1.73 m 2 . Conclusions: A paradigm shift from the FTM to the VTM in the prescription of incremental HD is proposed, whereby the VTM would allow less frequent treatments at lower Kru, with important clinical and economic implications. This approach is likely to be safe but needs to be confirmed by randomized controlled trials.

Incremental Hemodialysis, Residual Kidney Function, and Mortality Risk in Incident Dialysis Patients: A Cohort Study.

BACKGROUND: Maintenance hemodialysis is typically prescribed thrice weekly irrespective of a patient's residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis therapy initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF. STUDY DESIGN: A longitudinal cohort. SETTING & PARTICIPANTS: 23,645 patients who initiated maintenance hemodialysis therapy in a large dialysis organization in the United States (January 2007 to December 2010), had available RKF data during the first 91 days (or quarter) of dialysis, and survived the first year. PREDICTOR: Incremental (routine twice weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice weekly) hemodialysis regimens during the same time. OUTCOMES: Changes in renal urea clearance and urine volume during 1 year after the first quarter and survival after the first year. RESULTS: Among 23,645 included patients, 51% had substantial renal urea clearance (≥3.0mL/min/1.73m(2)) at baseline. Compared with 8,068 patients with conventional hemodialysis regimens matched based on baseline renal urea clearance, urine volume, age, sex, diabetes, and central venous catheter use, 351 patients with incremental regimens exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved renal urea clearance and urine volume at the second quarter, respectively, which persisted across the following quarters. Incremental regimens showed higher mortality risk in patients with inadequate baseline renal urea clearance (≤3.0mL/min/1.73m(2); HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline renal urea clearance (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in a subgroup defined by baseline urine volume of 600mL/d. LIMITATIONS: Potential selection bias and wide CIs. CONCLUSIONS: Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and is associated with greater preservation of RKF, whereas higher mortality is observed after the first year of dialysis in those with the lowest RKF. Clinical trials are needed to examine the safety and effectiveness of twice-weekly hemodialysis.

Incremental dialysis: two complementary views.

Franco Casino and Mariana Murea discuss today's knowledge about the 'incremental dialysis' concept. Franco Casino frames the problem by saying that, in the presence of substantial residual kidney function, kidney replacement therapy can begin with low doses and/or frequencies, to be gradually increased to compensate for any subsequent losses of residual kidney function, keeping the total clearance above the minimum levels of adequacy. He remarks that studies so far have documented that this approach is safe. He recognizes that adequate randomized controlled trials (RCTs) are necessary to confirm the safety and simplify and standardize the practical aspects of this approach. Mariana Murea objects that most of the evidence gathered so far primarily derives from retrospective and observational studies, which can be influenced by socioeconomic constraints. She argues for the need for RCTs to provide compelling empirical evidence on the efficacy of incremental dialysis. Nephrologists are still reluctant to adopt this approach for various reasons, including unfamiliarity with the method, lack of practical guidance and financial disincentives. Several countries have ongoing or planned RCTs comparing incremental dialysis with conventional dialysis. These trials can shift the haemodialysis paradigm if they validate the safety and effectiveness of this approach. The moderators believe that the results of ongoing trials must be carefully interpreted, and further validation may be needed across different patient populations or healthcare settings. The ultimate goal is to gather robust evidence that could lead to widespread adoption of incremental haemodialysis, optimizing treatment, reducing overtreatment, preserving resources and improving patients' quality of life.

Longitudinal Changes in Kidney Solute Clearance in a Prospective Cohort of Patients Initiating Chronic Hemodialysis.

Introduction: Longitudinal changes in residual kidney function have not been well-examined in patients starting chronic hemodialysis (HD). Methods: We analyzed urine volume and kidney solute clearances from timed urine collections and corresponding plasma samples from 42 patients randomized to incremental HD (n = 21) and conventional HD (n = 21) in the TwoPlus pilot study. Samples were collected before HD initiation (baseline); and at 6, 12, 24, and 48 weeks. We assessed temporal trends in urine volume, kidney urea and creatinine clearance, and correlations between urine volume and kidney solute clearance. Results: Residual kidney function parameters in all patients declined over time; the pattern of decline differed between urine volume and kidney solute clearances. Urine volume declined at a steady rate with median (quartile 1, quartile 3) percentage change relative to baseline of -10% (-36 to 29) at week 6 and -47% (-76 to 5) by week 48. Kidney urea and creatinine clearances exhibited a larger decline than urine volume at week 6, -32% (-61 to 8) and -47% (-57 to -20), respectively. The rate of decline subsequently slowed, reaching about 61% decline for both solutes by week 48. Conventional HD demonstrated larger declines in urine volume and kidney urea clearance than incremental HD at week 6. Urine volume showed moderate correlation with urea (R = 0.47) and weaker correlation with creatinine (R = 0.34). Conclusion: Despite gradual decrement in urine volume and kidney solute clearances, residual kidney function persists nearly 1 year after HD initiation. This knowledge could motivate increased practice of individualizing HD prescriptions by incorporating residual kidney function.

Average creatinine-urea clearance: revival of an old analytical technique?

Background: Creatinine-based equations such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are recommended for estimating glomerular filtration rate (eGFR) in clinical practice, but have reduced performance in advanced stages of chronic kidney disease. However, only rarely studies have evaluated the performance of eGFR by measuring the average of the urinary clearances of creatinine and urea (mClUN-cr) compared with the eGFR equations. Methods: This cross-sectional study evaluated the usefulness of mClUN-cr in a population of 855 participants who performed a GFR measurement by urinary inulin clearance. The performance of mClUN-cr was compared with those of CKD-EPI 2009 and CKD-EPI 2021, considering three criteria: bias, precision and accuracy. Results: In the whole sample, the mClUN-cr performed similarly to CKD-EPI equations (2009 and 2021) [precision: 11.5 (95% CI 10.5; 12.5) vs 19.0 (95% CI 17.2; 20.1) and 19.1 (95% CI 17.4; 20.4), and accuracy P30: 97.0 (95% CI 95.8; 98.0) vs 82.0 (95% CI 79.2; 84.4) and 77.2 (95% CI 74.5; 80.0)]. The CKD-EPI equations (2009 and 2021) had the best performance when mGFR was >60 mL/min/1.73 m2. In contrast, the mClUN-cr performed better than others with lowest mGFR values, more noticeable when mGFR was <60 mL/min/1.73 m2. Conclusions: The study described the best performance of mClUN-cr at GFR levels below 60 mL/min/1.73 m2 and a satisfactory result in the overall cohort. The findings point to a role of this tool, especially for estimating GFR in chronic kidney disease patients in developing countries, when reference measurement of GFR is not available.

Residual Kidney Function and Cause-Specific Mortality Among Incident Hemodialysis Patients.

Introduction: The survival benefit of residual kidney function (RKF) in patients on hemodialysis is presumably due to enhanced fluid management and solute clearance. However, data are lacking on the association of renal urea clearance (CLurea) with specific causes of death. Methods: We conducted a longitudinal cohort study of 39,623 adults initiating thrice-weekly in-center hemodialysis from 2007 to 2011 and had data on renal CLurea and urine volume. Multivariable cause-specific proportional hazards model was used to examine the associations between baseline RKF and cause-specific mortality, including sudden cardiac death (SCD), non-SCD cardiovascular death (CVD), and non-CVD. Restricted cubic splines were fitted for change in RKF over 6 months after initiating hemodialysis. Results: Among 39,623 patients with data on baseline renal CLurea and urine volume, there was a significant trend toward a higher mortality risk across lower RKF levels, irrespective of cause of death in a case-mix adjustment model (Ptrend < 0.05). Adjustment for ultrafiltration rate (UFR) slightly attenuated the association between low renal CLurea and high cause-specific mortality, whereas adjustment for highest potassium did not have substantial effect. Among 12,169 patients with data on change in RKF, a 6-month decline in renal CLurea showed graded associations with SCD, non-SCD CVD, and non-CVD risk, whereas the graded associations between faster 6-month decline in urine output and higher death risk were clear only for SCD and non-CVD. Conclusion: Lower RKF and loss of RKF were associated with higher cause-specific mortality among patients initiating thrice-weekly in-center hemodialysis.

Green synthesized nano-cellulose polyethylene imine-based biological membrane.

In hemodialysis process, membrane serves as a barrier between blood and the dialysate. The barrier when contacted by blood accompanied activation of coagulation, immunity, and cellular passageways. In the recent years, hemodialysis membrane's biocompatibility has become a issue which leads to reduce the performance during the separation process. In previous work, we developed and evaluated a cellulose-based membrane blended with polyaziridine or polyetyleneimine in formic acid for hydrophilicity, pure water flux, surface morphology, and permeation efficiency. Biocompatibility was accessed, by conducting cellular viability and cellular attachments tests. In this study, the membrane compared to a non-treated control, and cell viability revealed active and growing cell cultures after 14 days. During the cellular attachment experiment, cell cultures attached to the fabricated membrane simulated the formation of cell junctions, proving that the membrane is non-toxic and biocompatible. CA + PEI + FA membrane tested with a blood mimic fluid having density identical to renal patient's blood. The BSA concentration in the feed solution was the same as that in the blood of the renal patient. The results revealed that the CA + PEI + FA membrane was able to reject 99% bovine serum albumin (BSA) and 69.6% urea. Therefore, from biocompatibility and blood mimic fluid testing, it is confirmed that the CA + PEI + FA membrane is the finest implant for dialysis applications.

Could incremental haemodialysis be a new standard of care? A suggestion from a long-term observational study.

Introduction: The term incremental haemodialysis (HD) means that both dialysis dose and frequency can be low at dialysis inception but should be progressively increased, to compensate for any subsequent reduction in residual kidney function. Policy of the Matera Dialysis Center is to attempt an incremental start of HD without a strict low-protein diet in all patients choosing HD and with urine output (UO) >500 ml/day. The present study aimed at analyzing the results of this policy over the last 20 years. Subjects and methods: The dataset of all patients starting HD between January 1st, 2000 and December 31st, 2019 was retrieved from the local electronic database. Exclusion criteria were: urine output <500 ml/day or follow-up <3 months after the start of the dialysis treatment. Results: A total of 266 patients were retrieved; 64 of them were excluded from the study. The remaining 202 patients were enrolled into the study and subdivided into 3 groups (G1, G2 and G3) according to the frequency of treatment at the start of dialysis: 117 patients (57.9%) started with once-a-week (1HD/wk) (G1); 46 (22.8%) with twice-a-week (2HD/wk) (G2); 39 (19.3%) with thrice-a-week (3HD/wk) dialysis regimen (G3). Patients of G1 remained on 1HD/wk for 11.9 ±14.8 months and then transferred to 2HD/wk for further 13.0 ±20.3 months. Patients of G2 remained on 2HD/wk for 16.7 ±23.2 months. Altogether, 25943 sessions were administered during the less frequent treatment periods instead of 47988, that would have been delivered if the patients had been on 3HD/wk, thus saving 22045 sessions (45.9%). Gross mortality of the entire group was 12.6%, comparable to the mean mortality of the Italian dialysis population (16.2%). Survival at 1 and 5 years was not significantly different among the 3 groups: 94% and 61% (G1); 83% and 39% (G2); 84% and 46% (G3). Conclusions: Our long-term observational study suggests that incremental HD is a valuable option for incident patients. For most of them (80.7%) it is viable for about 1-2 years, with obvious socio-economic benefits and survival rates comparable to that of the Italian dialysis population. However, randomized controlled trials are lacking and therefore urgently needed. If they will confirm observational data, incremental HD will be a new standard of care.

Improving the "second generation Daugirdas equation" to estimate Kt/V on the once-weekly haemodialysis schedule.

INTRODUCTION: The haemodialysis (HD) dose, as expressed by Kt/V urea, is currently routinely estimated with the second generation Daugirdas (D2) equation (Daugirdas in J Am Soc Nephrol 4:1205-1213, 1993). This equation, initially devised for a thrice-weekly schedule, was modified to be used for all dialysis schedules (Daugirdas et al. in Nephrol Dial Transplant 28:2156-2160, 2013), by adopting a variable factor that adjusts for the urea generation (GFAC) over the preceding inter-dialysis interval (PIDI, days). This factor was set at 0.008 for the mid-week session of the standard thrice-weekly HD schedule. In theory, by setting PIDI = 7, one could get GFAC = 0.0025, to be used in patients on the once-weekly (1HD/wk) schedule, but actually this has never been tested. Moreover, GFAC was derived not taking into account the residual kidney urea clearance (Kru). Aim of the present study was to provide a specific value of GFAC for patients on  a once-weekly hemodialysis schedule. SUBJECTS AND METHODS: The equation to predict GFAC (GFAC-1) in the 1HD/wk schedule was established in a group of 80 historical Italian patients (group 1) and validated in a group of 100 historical Spanish patients (group 2), by comparing the Kt/V computed using GFAC-1 (Kt/VGFAC-1) with the reference Kt/V (Kt/VSS) values, as computed with the web-based Solute-Solver software (SS) (Daugirdas et al. in Am J Kidney Dis 54:798-809, 2009). Three more sets of Kt/V (Kt/V0.008, Kt/V0.0025 and Kt/V0.0035) values were computed using the GFAC of the original D2 equation (0.008), the GFAC predicted by PIDI/7 (0.0025) and the mean observed GFAC-1 (0.0035), respectively. They were compared with the reference Kt/VSS values. RESULTS: The predicting equation obtained from group 1 was: GFAC-1 = 0.0022 + 0.0105 × Kru/V (R2 = 0.93). Mean Kt/VSS in the group 2 was 1.54 ± 0.29 SD (N = 500 HD sessions). The mean percent differences for Kt/V0.008, Kt/V0.0025, Kt/VGFAC-1, and Kt/V0.0035 were 5.1 ± 1.0%, - 1.4 ± 0.7%, 0.0 ± 0.3%, - 0.3 ± 0.7%, respectively. No statistically significant difference was found between Kt/V values, except for Kt/V0.008. CONCLUSION: A linear relationship was found between GFAC and Kru/V in patients on the 1HD/wk schedule. Such a relationship is able to improve the "second generation Daugirdas equation" for an accurate estimate of the single pool Kt/V in this setting. However, a simple replacement in the D2 equation of 0.008 with the mean observed GFAC (0.0035) could suffice in the clinical practice.

The lacking equation that estimates the protein catabolic rate in patients on once-weekly haemodialysis.

BACKGROUND: The normalized protein catabolic rate (PCRn) is one of the key indices derived from the urea kinetic model (UKM) in haemodialysis (HD) patients. Ideally, it should be assessed using the double pool UKM (KDOQI clinical practice guidelines, AIKD, 2015), as the web-based software Solute-Solver (SS) does (Daugirdas et al., AJKD, 2009). Simple formulae exist to compute PCRn for patients on thrice- or twice-weekly HD schedule, but not for patients on once-weekly HD schedule (1HD/wk). Aim of the present technical note was to introduce the lacking equation that estimates PCRn in the 1HD/wk regimen. METHODS: Data of a single HD session associated to monthly UKM studies were retrieved from the electronic database of our dialysis unit for 80 historical patients on 1HD/wk regimen. The UKM parameters, as calculated with SS, were used in a subgroup of 40 randomly selected patients (group 1) to build-up a multiple regression model of PCRn. The latter was used to predict PCRn (PCRnPred) values in the cohort of the remaining 40 patients (group 2). The Bland-Altman plot was used to analyse the agreement between PCRnPred and the paired "observed" (PCRnObs) values, as measured with SS. RESULTS: The following equation was established by means of the multiple regression analysis: PCRn = - 0.46 + 0.01 × C0 + 0.09 × eKt/V + 3.94 × Kru/V, where C0 is pre-dialysis blood urea nitrogen concentration, eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. The PCRnPred values were 0.99 ± 0.24 g/kg/day; the PCRnObs values were 0.96 ± 0.23 g/kg/day (mean difference 0.03 ± 0.05 g/kg/day). Their difference at the Bland-Altman analysis ranged from - 0.08 to + 0.13 g/kg/day. Finally, a nomogram was drawn: it can be used to estimate not only PCRn from Kru/V and C0, but also C0 as a function of Kru/V and PCRn. CONCLUSIONS: The equation here introduced allows a simple and accurate estimate of PCRn in patients on once-weekly HD regimen. The availability of the nomogram relating C0 to PCRn and Kru/V could be a further step to make safer and safer the once-weekly HD regimen. The following equation was established by means of the multiple regression analysis [Formula: see text] where PCRn is the normalized protein catabolic rate (PCRn), C0 is pre-dialysis blood urea nitrogen concentration (BUN), eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. A nomogram relating pre-dialysis BUN to PCRn and Kru/V could be drawn: it can be used to estimate not only PCRn from Kru/V and pre-dialysis BUN, but also pre-dialysis BUN as a function of Kru/V and PCRn.

Case Report: Subtherapeutic Vancomycin and Meropenem Concentrations due to Augmented Renal Clearance in a Patient With Intracranial Infection Caused by Streptococcus intermedius.

Streptococcus intermedius occasionally causes brain abscesses that can be life-threatening, requiring prompt antibiotic and neurosurgical treatment. The source is often dental, and it may spread to the eye or the brain parenchyma. We report the case of a 34-year-old man with signs of apical periodontitis, endophthalmitis, and multiple brain abscesses caused by Streptococcus intermedius. Initial treatment with meropenem and vancomycin was unsuccessful due to subtherapeutic concentrations, despite recommended dosages. Adequate concentrations could be reached only after increasing the dose of meropenem to 16 g/day and vancomycin to 1.5 g × 4. The patient exhibited high creatinine clearance consistent with augmented renal clearance, although iohexol and cystatin C clearances were normal. Plasma free vancomycin clearance followed that of creatinine. A one-day dose of trimethoprim-sulfamethoxazole led to an increase in serum creatinine and a decrease in both creatinine and urea clearances. These results indicate that increased tubular secretion of the drugs was the cause of suboptimal antibiotic treatment. The patient eventually recovered, but his left eye needed enucleation. Our case illustrates that augmented renal clearance can jeopardize the treatment of serious bacterial infections and that high doses of antibiotics are needed to achieve therapeutic concentrations in such cases. The mechanisms for regulation of kidney tubular transporters of creatinine, urea, vancomycin, and meropenem in critically ill patients are discussed.

Routine assessment of kidney urea clearance, dialysis dose and protein catabolic rate in the once-weekly haemodialysis regimen.

BACKGROUND: The dialysis dose (Kt/V) and normalized protein catabolic rate (PCRn) are the most useful indices derived from the urea kinetic model (UKM) in haemodialysis (HD) patients. The kidney urea clearance (Kru) is another important UKM parameter which plays a key role in the prescription of incremental HD. Ideally, the three kinetic parameters should be assessed using the complex software Solute Solver based on the double pool UKM. In the clinical setting, however, the three indices are estimated with simplified formulae. The recently introduced software SPEEDY assembles the aforementioned equations in a plain spreadsheet, to produce quite accurate results of Kru, Kt/V and PCRn. Unfortunately, specific equations to compute Kt/V and PCRn for patients on a once-weekly HD regimen (1HD/wk) were not available at the time SPEEDY was built-up. We devised a new version of SPEEDY (SPEEDY-1) and an even simpler variant (SPEEDY-1S), using two recently published equations for the 1HD/wk schedule . Moreover, we also added a published equation to estimate the equivalent renal clearance (EKR) normalized to urea distribution volume (V) of 35 L (EKR35) from Kru and Kt/V . Aim of the present study was to compare the results obtained using the new methods (SPEEDY-1 and SPEEDY-1S) with those provided by the reference method Solute Solver. SUBJECTS AND METHODS: One hundred historical patients being treated with the once-weekly HD regimen were enrolled. A total of 500 HD sessions associated to the availability of monthly UKM studies were analysed in order to obtain Kru, single pool Kt/V (spKt/V), equilibrated Kt/V (eKt/V), V, PCRn and EKR35 values by using Solute Solver, SPEEDY-1 and SPEEDY-1S. RESULTS: When comparing the paired values of the above UKM parameters, as computed by SPEEDY-1 and Solute Solver, respectively, all differences but one were statistically significant at the one-sample t-test; however, the agreement limits at Bland-Altman analysis showed that all differences were negligible. When comparing the paired values of the above UKM parameters, as computed by SPEEDY-1S and Solute Solver, respectively, all differences were statistically significant; however, the agreement limits showed that the differences were negligible as far as Kru, spKt/V and eKt/V are concerned, though much larger regarding V, PCRn and EKR35. CONCLUSIONS: We implemented SPEEDY with a new version specific for the once-weekly HD regimen, SPEEDY-1. It provides accurate results and is presently the best alternative to Solute Solver. Using SPEEDY-1S led to a larger difference in PCRn and EKR35, which could be acceptable for clinical practice if SPEEDY-1 is not available.

Sodium loss, extracellular volume overload and hypertension in peritoneal dialysis patients treated by automated peritoneal dialysis cyclers.

INTRODUCTION: Achieving sodium balance is important for peritoneal dialysis patients, as sodium excess may lead to hypertension and extracellular water expansion. We wished to determine whether greater sodium removal had adverse consequences. METHODS: We calculated 24-h urinary and peritoneal sodium losses in peritoneal dialysis patients treated by automated cyclers, when attending for peritoneal membrane and bioimpedance assessments. RESULTS: We reviewed 439 peritoneal dialysis patients, 56.7% male, average age 54.6 years, median sodium loss 110 (68-155) mmol/day. Sodium loss was strongly associated with urine volume, r = 0.37, protein nitrogen appearance rate, r = 0.29, and body cell mass, r = 0.21, all p < 0.001. We found no association with blood pressure or anti-hypertensive medication prescription, or extracellular water. On multivariable logistic regression analysis, sodium loss was associated with greater urine output, odds ratio 1.001, 95% confidence interval 1.00-1.001, p < 0.001, and protein nitrogen appearance (odds ratio 1.023, confidence interval 1.006-1.04), p = 0.008. Adjusting for body weight, sodium loss was associated with urine output (odds ratio 1.001, confidence interval 1.001-1.002, p < 0.001), and negatively with body fat index (odds ratio 0.96, confidence interval 0.93-0.99, p = 0.008) and co-morbidity grade (odds ratio 0.58, confidence interval 0.36-0.39, p = 0.023). CONCLUSION: Heavier peritoneal dialysis patients with greater estimated dietary protein intake (protein nitrogen appearance), those with greater residual renal function and peritoneal clearances, along with lower co-morbidity, had greater daily sodium losses. Adjusting for body weight, then sodium losses were greater with higher daily urine output, and lower in patients with proportionately more body fat and co-morbidity. Sodium losses would appear to primarily determined by body size and not associated with hypertension or extracellular water expansion.