Renal Creatinine Clearance Research Articles

Linking clinical manifestations and causative organisms may provide clues for the treatment of peritoneal dialysis-associated peritonitis

IntroductionDifferent initial manifestations of peritoneal dialysis-associated peritonitis (PDAP) may depend on the type of pathogenic organism. We investigated the association between the clinical characteristics of PDAP and susceptibility to vancomycin and investigated the possibility of using vancomycin monotherapy alone as an initial treatment regimen for some PDAP patients to avoid unnecessary antibiotic exposure and secondary infection.MethodsPatients with culture-positive PDAP were retrospectively analyzed and divided into two groups: peritonitis with only cloudy effluent (PDAP-cloudy) or with cloudy effluent, abdominal pain and/or fever (PDAP-multi). The bacterial culture of PD effluent and antibiotic sensitivity test results were compared between groups. Logistic regression was used to investigate factors predicting susceptibility to vancomycin.ResultsOf 162 episodes of peritonitis which had a positive bacterial culture of PD fluid, 30 peritonitis were in the PDAP-cloudy group, and 132 peritonitis were in the PDAP-multi group. Thirty (100%) peritonitis in the PDAP-cloudy group had gram-positive bacterial infections, which was significantly greater than that in the PDAP-multi group (51.5%) (P < 0.001). Twenty-nine (96.7%) peritonitis in the PDAP-cloudy group were susceptible to vancomycin, compared to 67 (50.8%) in the PDAP-multi group (P < 0.001). The specificity of PDAP-cloudy for vancomycin-sensitive peritonitis was 98.48%. Only one patient (3.3%) in the PDAP-cloudy group experienced vancomycin-resistant peritonitis caused by Enterococcus gallinarum, which could neither be covered by vancomycin nor by the initial antibiotic regimen recommended by the current ISPD guidelines. The presence of only cloudy effluent was an independent predictor of susceptibility to vancomycin according to multivariate analysis (OR = 27.678, 95% CI 3.191-240.103, p = 0.003), in addition to PD effluent WBC counts (OR = 0.988, 95% CI 0.980–0.996, p = 0.004), diabetes mellitus (OR = 3.646, 95% CI 1.580–8.416, p = 0.002), first episode peritonitis (OR = 0.447, 95% CI 0.207–0.962, p = 0.039) and residual renal creatinine clearance (OR = 0.956, 95% CI 0.918–0.995, p = 0.027). Addition of these characteristics increased the AUC to 0.813 (95% CI 0.0.749–0.878, P < 0.001). The specificity of presenting with only cloudy effluent for vancomycin-sensitive peritonitis was 98.48%.ConclusionsCloudy dialysate, as the only symptom at PDAP onset, was an independent predictor of vancomycin-sensitive PDAP, which is an important new insight that may guide the choice of initial antibiotic treatment.

Effect of a Triterpenoid-Rich Olive Oil on Chronic Kidney Disease in an Experimental Model of Diabetes Mellitus.

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus.

The efficacy of sacubitril/valsartan in patients receiving peritoneal dialysis with diabetes and heart failure with preserved ejection fraction.

To investigate the efficacy of sacubitril/valsartan in the treatment of peritoneal dialysis (PD) in patients with diabetes and heart failure with preserved ejection fraction (HFpEF). Patients with diabetes who underwent PD and had HFpEF (n = 64) were divided into two groups: the experimental group (n = 31), which was administered sacubitril/valsartan, and the control group (n = 33), administered valsartan alone. Data were collected before and after treatment to compare the inter-group changes in cardiac function indexes, residual renal function (RRF), and PD adequacy indexes. Compared with the control group, the N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were lower in the experimental group after treatment (Wilcoxon test, p < 0.05). The descent ranges of NT-proBNP, left ventricular end-systolic dimension, and left ventricular fraction shortening, as well as increases in the amplitude of left ventricular ejection fraction after treatment were better in the experimental group than in the control group (t-test, p < 0.05). The descent ranges of residual renal glomerular filtration rate, residual renal Kt/Vurea, and residual renal creatinine clearance, as well as increases in the amplitude of β2-microglobulin, were lower in the experimental group than in the control group (Wilcoxon test, p < 0.05). However, there were no significant differences between the two groups in the descent ranges of the PD adequacy indexes (Wilcoxon test, p > 0.05). Hyperkalemia occurred in 8 cases (25.81%) in the experimental group and 13 cases (39.39%) in the control group, while hypotension occurred in 2 cases (6.45%) and 1 case (3.03%), respectively. No other adverse effects were observed in either group. The findings suggest that sacubitril/valsartan can safely and effectively improve RRF and cardiac function in patients with diabetes combined with HFpEF receiving PD, but it has little effect on PD adequacy.

Effect of onions tunic extract on sodium oxalate-induced acute kidney injury

Acute kidney injury (AKI) is one of the global health concerns afflicting the human population and urolithiasis (kidney stone), especially the calcium oxalate stone is the most prominent amongst the stone formers with a huge recurrence rate. This study elucidates the ameliorative potential of the tunic of onions against Wistar kidney rats toxified with sodium oxalate.Ethylacetate extract of the tunic of onions otherwise regarded as Onions peel extract (OPE) in this study was prepared to get the flavonol-rich extracts. Adult male Wistar rats received 70 mg/kg body weight sodium oxalate with or without co-treatment with OPE, quercetin or cystone. Biochemical analyses were carried out on the plasma and urine, followed by a histopathological assessment of the kidney. Intoxication with sodium oxalate brought about electrolyte imbalance, nephrotic syndrome (high concentrations of total protein and albumin in the urine and low concentrations in the plasma) reduced renal function (low renal clearance of creatinine and urea) and damage to the kidney as well as fluid accumulation. Treatment with flavonol extract from onion tunic mitigated these deleterious changes as a result of sodium oxalate intoxication. The finding suggests that onion peel has the potential to prevent damage arising from oxalate toxicity in the kidney.Graphical

A real-world analysis of safety profile of selexipag by using FDA adverse Event Reporting System (FAERS)

ABSTRACT Background The current investigation sought to conduct a real-world analysis of adverse events (AEs) associated with selexipag by utilizing data from the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods The Reporting Odds Ratios (ROR) and the Medicines Healthcare Products Regulatory Agency (MHRA) method were employed to assess the potential associations between selexipag and AEs. Case reports of adverse drug reaction (ADR) related to selexipag were systematically sourced from PubMed, Embase, and Web of Science databases. Results Our analysis identified 281 Preferred Terms (PTs) signals across 20 System Organ Classes (SOCs) were found to meet the screening threshold. The most common AEs were consistent with instructions, randomized controlled trials (RCTs), and case reports. Of significant note, unexpected AEs principally target SOCs of infections and infestations, blood and lymphatic system, renal and urinary disorders, hepatobiliary disorders, including pneumonia, metapneumovirus, decreased hemoglobin. transfusion, iron-deficiency anemia, dialysis hypotension, abnormal creatinine renal clearance, liver function test increased, hepatic function abnormal, hepatic enzyme increased. Within the pediatric population, unexpected signals such as pyrexia, pneumonia, and intussusception necessitate special precautionary measures. Conclusions The findings contribute valuable insights to clinical practice, reinforcing the importance of vigilant monitoring, and can be instrumental in guiding both therapeutic applications and safety assessments of this particular medication.

Acute renal failure during cisplatin-based chemotherapy: A prospective monocentric study.

Cisplatin is a widely used antineoplastic in the treatment of various types of solid cancers. The objectives of our study were to evaluate the prevalence of acute renal failure (ARF) during cisplatin-based chemotherapy and to determine the factors correlated with renal toxicity. This is a prospective study that was conducted over a period of 6 months. We included patients followed for histologically confirmed solid cancer and treated with cisplatin-based chemotherapy. Assessment of renal function was made by calculating renal creatinine clearance before starting cisplatin, before every cycle, at 3 months and at 6 months. Forty patients were included. The median age was 54 years (31-71 years). The mean cumulative dose received was 286 mg/m² (100-560 mg/m²). Twelve patients (30%) developed ARF which was grade 1 in 83% of cases. Cisplatin ARF was observed after a mean cumulative dose of 208 mg/m². Digestive toxicity (67%) and obstruction of the excretory tracts of tumoral origin (8%) were aggravating factors. Cisplatin cycle number >3 (p = 0.04) and dose ≥330 mg/m2 (p = 0.04) were the factors associated with cisplatin renal toxicity. This study concluded that ARF is dose-dependent with the predominance of grade 1 toxicity. A cumulative dose exceeding 330 mg/m2 was correlated with an increased risk of occurrence of ARF.

Effects of Pegagan Embun (Hydrocotyle sibthorpioides Lam) Extract on Renal Function in Male Wistar Rats as Assessed by Creatinine Clearance

In Indonesia, pegagan embun (Hydrocotyle sibthorpioides Lam), a low-growing plant native to southeastern Asia, has been used as a traditional medicine to treat numerous ailments. However, additional research on the safety of this plant is needed, particularly before it can be promoted as a potential immune system-boosting drug. The present study aimed to evaluate the sub-acute toxicity effects of ethanol extract of Hydrocotyle sibthorpioides (HS) on renal function. Thirtysix male Wistar rats divided into four groups were used for this study. The control group was given NaCMC (0.5%), and the three treatment groups received an oral dose of the extract of HS at doses of 7, 35, and 150 mg/kg BW, respectively, for 21 days. The parameters measured include: 24-hour urine volume, serum creatinine, urine creatinine, creatinine clearance, and the percentage of renal function on the 7th, 14th, and 21st days were determined. The results showed that doses of HS extract at 7, 35, and 150 mg/kg BW significantly affected creatinine clearance (p&lt;0.05). In contrast, the duration of administration has no significant effect on creatinine clearance (p&gt;0.05). Renal function increased above the standard value (&gt;100%) at 7 and 35 mg/kg BW doses. Thus, these concentrations could potentially cause impairments in renal function. The study concludes that various doses of the ethanol extract of Hydrocotyle sibthorpioides affected renal creatinine clearance in Wister rats. In contrast, the duration of administration of Hydrocotyle sibthorpioides extract did not affect creatinine clearance in the test animals.

Relationship Between Peritoneal Protein Clearance and Hemoglobin in Peritoneal Dialysis Patients: A Prospective Cohort Study

The relationship between higher peritoneal protein clearance (PPCl) and hemoglobin (Hb) levels in peritoneal dialysis (PD) patients is unknown. We explored this relationship and interaction on all-cause mortality in this prospective cohort study with a large number of PD patients. We enrolled prevalent PD patients in a single PD center. Demographic characteristics and clinical and biochemical data were collected. The total amount of protein loss in the dialysate and PPCl corrected for serum albumin were calculated. The primary study endpoint was all-cause mortality. We examined the relationship between PPCl, Hb, and all-cause mortality in the Cox regression model. We included a total of 487 PD patients (58.3% males, mean age 49.5±14.9years). The median PD duration at enrollment was 30.1 (15.8-48.3) months. Mean Hb level was 11.1±1.9g/dL, and 221 (45.3%) patients had Hb levels <11g/dL. Patients with Hb<11g/dL had lower serum albumin, lower residual renal creatinine clearance, and higher PPCl. In a multilinear regression model, PPCl (β=-0.12, P=.015) had an independent negative linear association with Hb levels. In the logistic regression model, higher PPCl was independently associated with lower Hb (<11g/dL) (odds ratio=1.02; 95% confidence interval [CI]: 1.01-1.03). In the overall cohort, after adjusting for confounders in the Cox regression model, decrease in Hb level was independently associated with increased risk (hazard ratio: 0.86, 95% CI: 0.77-0.95) of all-cause mortality. Interaction-effect test showed that PPCl influenced the relationship between Hb level and all-cause mortality (P=.011). After adjusting for confounders, lower Hb level was independently associated with a higher risk (hazard ratio: 0.85, 95% CI: 0.74-0.97) of all-cause mortality only in patients with PPCl ≥59.5mL/day and not in patients with lower PPCl. Higher PPCl was an independent predictive factor of lower Hb levels in PD patients. Therefore, PPCl influenced the relationship between Hb level and all-cause mortality in PD patients.

Clinical assessment of gepotidacin (GSK2140944) as a victim and perpetrator of drug-drug interactions via CYP3A metabolism and transporters.

Gepotidacin is a novel triazaacenaphthylene antibiotic in phase III development. Based on nonclinical in vitro characterization of gepotidacin metabolism, two phase I studies were conducted in healthy participants to investigate clinical drug-drug interactions (DDIs). We assessed gepotidacin as a DDI victim with a potent cytochrome P450 (CYP) 3A4/P-glycoprotein (P-gp) inhibitor (itraconazole), potent CYP3A4 inducer (rifampicin), and nonspecific organic cation transporter (OCT)/multidrug and toxic extrusion transporter (MATE) renal transport inhibitor (cimetidine) via single doses of gepotidacin before and after co-administration with multiple doses of the modulator drugs. Gepotidacin DDI perpetrator potential for P-gp inhibition (digoxin) and CYP3A4 inhibition (midazolam) was evaluated via single doses of the two-drug cocktail without and with gepotidacin. The DDI magnitudes were interpreted based on area under the concentration-time curve (AUC). A weak DDI (AUC increase 48%-50%) was observed for gepotidacin co-administered with itraconazole. A clinically significant decrease in gepotidacin plasma AUC (52%) was observed with rifampicin coadministration, indicating a moderate DDI. There was no DDI for gepotidacin with cimetidine; a unique biomarker approach showed increased serum creatinine (24%), decreased renal clearance of creatinine (21%), and N1-methylnicotinamide (39%), which confirmed extensive MATE inhibition and partial OCT2 inhibition. Gepotidacin was not a P-gp DDI perpetrator, although the maximum plasma concentration of digoxin increased (53%) and is potentially clinically relevant given its narrow therapeutic index. Gepotidacin demonstrated weak CYP3A4 inhibition with midazolam (<2-fold AUC increase). There were no new safety-risk profile findings. These results will inform the safe and efficacious clinical use of gepotidacin when co-administered with other drugs.

Augmented renal clearance in the ICU: estimation, incidence, risk factors and consequences—a retrospective observational study

BackgroundAugmented renal clearance (ARC) remains poorly evaluated in ICU. The objective of this study is to provide a full description of ARC in ICU including prevalence, evolution profile, risk factors and outcomes.MethodsThis was a retrospective, single-center, observational study. All the patients older than 18 years admitted for the first time in Medical ICU, Bichat, University Hospital, APHP, France, between January 1, 2017, and November 31, 2020 and included into the Outcomerea database with an ICU length of stay longer than 72 h were included. Patients with chronic kidney disease were excluded. Glomerular filtration rate was estimated each day during ICU stay using the measured creatinine renal clearance (CrCl). Augmented renal clearance (ARC) was defined as a 24 h CrCl greater than 130 ml/min/m2.Results312 patients were included, with a median age of 62.7 years [51.4; 71.8], 106(31.9%) had chronic cardiovascular disease. The main reason for admission was acute respiratory failure (184(59%)) and 196(62.8%) patients had SARS-COV2. The median value for SAPS II score was 32[24; 42.5]; 146(44%) and 154(46.4%) patients were under vasopressors and invasive mechanical ventilation, respectively. The overall prevalence of ARC was 24.6% with a peak prevalence on Day 5 of ICU stay. The risk factors for the occurrence of ARC were young age and absence of cardiovascular comorbidities. The persistence of ARC during more than 10% of the time spent in ICU was significantly associated with a lower risk of death at Day 30.ConclusionARC is a frequent phenomenon in the ICU with an increased incidence during the first week of ICU stay. Further studies are needed to assess its impact on patient prognosis.

In The Absence Of Cardiometabolic Diseases Is Age An Independent Factor In Assessing Renal Health And Function? A Pilot Study

Estimated glomerular filtration rate (eGFR) is a measure of renal filtration and clearance of serum creatinine and is conventionally used to characterize the progressive decline in renal function (RF). Assessment of RF and renal health (RH) is traditionally believed to be age-dependent. However, in the absence of cardiometabolic diseases (hypertension, diabetes, hyperlipemia, etc.), this may not be the case. Recently, novel markers of RH and RF support the notion that age is a secondary factor influencing renal decline. PURPOSE: To determine the magnitude of age as an influencing factor involved in the decline of RF with novel markers of RH and function in the absence of cardiometabolic risk factors. METHODS: Fifty-four participants (n = 27 men; n = 27 women; age 33.4 + 12.5 yr; height 171.7 + 10.9 cm; weight 77.9 + 15.9 kg; BMI 26.5 + 5.5; SBP 120 + 10.4; DBP 77.7 + 6.7; CHOL 174 + 30; and GLU 95 + 7) completed a single health assessment to quantify renal health and function. Blood and urine samples were collected by the same technician under standardized conditions and stored at -80 °C until project completion. Serum creatinine (sCR), urine creatinine (uCr), cystatin C (CyC), and urine epidermal growth factor (uEGF) were used to calculate estimates of renal health and function via uEGF/uCr ratio (uEGFR), eGFR - modification of diet in renal disease (MDRD), CKD-EPI, and SCr/CyC eGFR. Renal health and function markers were analyzed and compared in age groups (20s, 30s, 40s, 50s) using 4 (group) by 1 (sample) ANOVAs. RESULTS: There were no significant differences between age groups in the biomarkers and estimates of RH and RF. sCR (F = 0.17, p = 0.91), uEGF (F = 0.87, p = 0.46), CyC (F = 1.98, p = 0.13), CyC eGFR (F = 2.81, p = 0.10), MDRD (F = 2.08, p = 0.12), CKD-EPI (F = 0.34, p = 0.80), and SCr/CyC eGFR (F = 2.05, p = 0.12). uEGFR was significantly different between (F = 1.93, p = 0.14) different between age groups. uCr was significantly different ((F = 5.33, p = 0.003) between 40s and 50s. CONCLUSION: Changes in RH and RF appear to be independent of age in the absence of cardiometabolic diseases, indicates RH and RF could potentially be maintained in adulthood, middle age, and possibly attenuated in the senior years with the continued absence of cardiometabolic diseases.

MO703URINE VOLUME AS A MARKER OF RESIDUAL KIDNEY FUNCTION IN PERITONEAL DIALYSIS PATIENTS: QUANTITATIVE ASSESSMENT

Abstract Background and Aims In dialysis patients, urine volume is an easy-to-obtain marker of residual kidney function but information is lacking of its potential value as an estimate of the renal contribution to total clearance of small solutes. We explored whether correlations of urine volume with different estimations of the residual renal function for urea, creatinine, and phosphorus, could be used to assess renal solute clearances and renal mass removal for investigated solutes. Method In an observational study of 94 non-anuric (urine output ≥ 100 mL per 24 hours) patients (54% men, median age 59 [45 - 68] year, BMI 25.8 [21.4 - 27.7] kg/m2) undergoing automated (n = 59) or continuous ambulatory (n = 35) peritoneal dialysis (PD), we evaluated renal, peritoneal and total (renal plus peritoneal) solute removal (g/week) and clearance (L/week) in relation to urine volume (L/day). Urine volume, renal clearances, ratio of urine solute to serum solute concentration, removed mass of each solute and the ratio of mass removed by urine (renal clearance) over total mass removed by urine and dialysate (total clearance) for urea, creatinine and phosphorus were estimated from 24 h collections of urine and dialysate and determination of solute concentrations in serum, urine and dialysate. Statistical dependence between variables was tested using Spearman’s correlation coefficient (rho). Data are expressed as median with interquartile range. Results Median 24-hour urine output was 560 [323 – 938] mL. Renal mass removal for urea, creatinine and phosphorus was 10.1 [4.5 – 17.1], 3.5 [1.8 – 5.6] and 1.0 [0.4 – 1.7] g/week, respectively. The average contribution of residual renal removal to the total mass removed was 28% [17% - 41%] for urea, 56% [30% - 72%] for creatinine and 44% [24% - 58%] for phosphorus. Serum creatinine correlated weakly and negatively with urine volume (rho = -0.26, p &amp;lt; 0.05), but no such relationship was observed for urea and phosphorus. Only urine concentration of creatinine correlated weakly with urine volume with rho = -0.28 and p &amp;lt; 0.01. Urine concentration over plasma concentration did not correlate with urine volume for any solute. Renal urea clearance (20.1 [11.4 - 35.7] L/week) correlated positively with creatinine renal clearance (43.0 [18.9 - 75.1] L/week), (rho = 0.92), and with phosphorus renal clearance (17.3 [7.6 - 32.9] L/week), (rho = 0.89, p &amp;lt; 0.001; Fig. 1A), while renal creatinine clearance correlated positively with phosphorus renal clearance (rho = 0.86, p&amp;lt;0.001). Urine volume correlated positively with urea, creatinine and phosphorus clearances at rho 0.78, 0.63 and 0.73, respectively (all p&amp;lt; 0.001), and with renal removal of mass of urea, creatinine, and phosphorus with rho= 0.83, 0.68 and 0.74 (Fig. 1B), respectively; all p&amp;lt;0.001. Conclusion In PD patients, solute renal clearances and renal mass removal for urea, creatinine and phosphorus may be predicted from urine volume. Among renal clearances for urea, creatinine, and phosphorus two of them may be assessed based on measurements of the third one.

MO696INCREMENTAL PERITONEAL DIALYSIS: BENEFICIAL EFFECTS

Abstract Background and Aims Incremental peritoneal dialysis (Incr_Dial) is a renal replacement therapy strategy based on lower dose prescription rather than the standard “full dose” (Full_Dial). Individualized clearance goals were achieved combining residual renal function (RRF) and peritoneal clearance. Maintaining RRF is a crucial issue to peritoneal dialysis (PD) patients and the best PD strategy to preserve it is subject to debate. The aim of this study is to compare Incr_Dial and Full_Dial in terms of RRF preservation and other clinical outcomes. Method This was a single-center, retrospective descriptive study. We included a cohort of incident and prevalent adult PD patients in the PD Unit between January – December of 2020. Patients without a follow-up &amp;lt; six months and who started PD at another center were excluded. Patients were assigned according to their first PD protocol in two groups – Group A: Incr_Dial protocol (continuous ambulatory PD: less than four dwells daily, less than 2 L dwell volumes, less than seven days a week treatment, or some combination of these; automated PD: without a long dwell, less than 10 L daily delivered by cycler and day dwells, treatment for less than 7 days a week or some combination of these); Group B: Full_Dial protocol. Statistical analysis was performed using SPSS 20.0. Statistical significance level p &amp;lt;0.05. Results Among 84 PD patients, 68% underwent incremental PD (Group A) and 31% underwent conventional full-dose PD (Group B). The mean age was 55.9±15.4 years, 60.7% were male and 32.5% diabetic. There were no statistically significant differences between the two groups regarding: demographic characteristics, comorbidities (diabetes, hypertension, cardiac insufficiency or ischemic heart disease) and drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and/or loop diuretics). The median Incr_Dial duration to achieve PD full dose was 10.2 months (IQ 5.1-17). At the beginning of PD, there was no statistically significant difference in diuresis between both groups (A: 1.79L vs B: 1.2L, p=0.07), however after 6 months of PD there was a superior urinary output in Group A (A: 1.67L vs B: 1.1L, p=0.037). Group A (Incr_Dial) was also associated with a superior renal clearance of creatinine at the beginning (A: 81 L/sem/1.73m2 vs B: 56.8L/sem/1.73m2, p=0.021) and after 12 months (A: 70.7L/sem/1.73m2 vs B: 26.3 L/sem/1.73m2, p&amp;lt;0.01); and superior Kt/V renal/week at the beginning (A: 1.48 vs B: 1.02, p=0.02) and after 12 months (A: 1.28 vs B: 0.49, p&amp;lt;0.001). There are no differences between mortality (A: 1.9% vs B: 12%, p=0.094), peritonitis-free time (A: 158 days vs B: 236 days, p=0.133) and the numbers of peritonitis per year (A: 0.32 vs B: 0.5, p=0.940). However, the rate of hospital admissions per year was lower in Group A (A: 0.22 vs B: 0.70, p=0.001). Conclusion Incremental PD is a safe strategy of renal replacement therapy to start PD. In our PD population, it showed similar patient survival rates and a significantly less hospital admissions. Incremental PD was also beneficial for preserving RRF when compared to full-dose PD.

The effect of high-dose, short-term caffeine intake on the renal clearance of calcium, sodium and creatinine in healthy adults.

The consumption of caffeine has been linked to osteoporosis, believed to be due to enhanced bone resorption as a result of increased calcium excretion in the urine. However, the amount of calcium in the urine may not necessarily reflect the true effect of caffeine on calcium clearance. This study therefore examined the impact of high-dose, short-term caffeine intake on renal clearance of calcium, sodium and creatinine in healthy adults. In a double-blind clinical study, participants chewed caffeine (n = 12) or placebo (n = 12) gum for 5 minutes at 2-hour intervals over a 6-hour treatment period (800 mg total caffeine). Caffeine increased renal calcium clearance by 77%. Furthermore, the effect was positively correlated with sodium clearance and urine volume, suggesting that caffeine may act through inhibition of sodium reabsorption in the proximal convoluted tubule. This study confirmed that caffeine does increase renal calcium clearance and fosters further investigation into safe consumption of caffeine.

Evaluation of glomerular filtration rate using iohexol plasma clearance in critically ill patients with augmented renal creatinine clearance: A single-centre retrospective study.

Augmented renal creatinine clearance (ARC) (≥130 ml min-1 1.73 m-2) is frequent in intensive care unit (ICU) patients and may impact patient outcome. To compare glomerular filtration rate (GFR) measured with iohexol plasma clearance and creatinine clearance in critically ill patients with augmented renal clearance. Single-centre, retrospective study. French University Hospital ICU from November 2016 to May 2019. Adult patients with augmented renal clearance who had a measurement of iohexol plasma clearance. Agreement between 6 h creatinine clearance (6 h CrCl) and iohexol plasma clearance (GFRio). Twenty-nine patients were included. The median 6 h creatinine clearance was 195 [interquartile range (IQR) 162 to 251] ml min-1 1.73 m-2 and iohexol clearance was 133 [117 to 153] ml min-1 1.73 m-2. Sixteen patients (55%) had hyperfiltration (clearance >130 ml min-1 1.73 m-2) measured with iohexol clearance. Mean bias between iohexol and creatinine clearance was -80 [limits of agreement (LoA) -216 to 56 ml min-1 1.73 m-2]. For Cockcroft and Gault Modification of Diet in Renal Disease equation (MDRD), Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) formulae, mean biases were, respectively -27 (LoA -99 to 45), -14 (LoA -86 to 59) and 15 (LoA -33 to 64) ml min-1 1.73 m-2. In the present study, we found that in patients with augmented renal creatinine clearance, half of the patients do not have hyperfiltration using iohexol clearance measurements. We observed an important bias between 6 h CrCl and GFRio with large LoA. In critically patients with ARC, 6 h CrCl does not reliably estimate GFR and 6 h CrCl nearly systematically overestimates renal function. Comparison of creatinine-based GFR estimations and GFRio show acceptable bias but wide LoA.

Beta-trace protein as a potential biomarker of residual renal function in patients undergoing peritoneal dialysis

BackgroundResidual renal function is closely linked to quality of life, morbidity and mortality in dialysis patients. Beta-trace protein (BTP), a low molecular weight protein, has been suggested as marker of residual renal function, in particular in patients on hemodialysis. We hypothesized that BTP also serves as a marker of residual renal function in pertioneal dialysis patients.MethodsIn this study 34 adult patients on peritoneal dialysis were included. BTP, creatinine, cystatin C and urea concentrations were analyzed simultaneously in serum and dialysate to calculate renal and peritoneal removal of the analytes.ResultsIn peritoneal dialysis patients with residual diuresis, mean serum BTP was 8.16 mg/l (SD ± 4.75 mg/l). BTP correlated inversely with residual diuresis (rs = − 0.58, p < 0.001), residual creatinine clearance (ClCr) (rs = − 0.69, p < 0.001) and total urea clearance (Clurea) (rs = − 0.56, p < 0.001). Mean peritoneal removal of BTP was 3.36 L/week/1.73m2 (SD ± 1.38) and mean renal removal 15.14 L/week/1.73m2 (SD ± 12.65) demonstrating a significant renal contribution to the total removal. Finally, serum BTP inversely correlated with alterations in residual diuresis (r = − 0.41, p = 0.035) and renal creatinine clearance over time (r = − 0.79, p = p < 0.001).ConclusionBTP measurement in the serum may be a simple tool to assess residual renal function in peritoneal dialysis patients.

Prognostic impact of renal function trajectories and temporal variability amongst anticoagulated atrial fibrillation patients: a subgroup analysis of the SPORTIF III and V trials

Abstract Background Renal function is a major determinant of major adverse outcomes in patients with atrial fibrillation (AF). Scarce data are available about the impact of renal function trajectories and creatinine clearance (CrCl) temporal variability, on prognosis. Aim To evaluate the progression and impact of renal function impairment and variability on outcomes over a long-term follow-up observation in a cohort of anticoagulated AF patients. Methods We included warfarin-treated AF patients in SPORTIF trials with available creatinine clearance (according to Cockroft-Gault) at baseline and at least 4 evaluations throughout their follow-up. Patients with a BMI ≥45 kg/m2 were excluded from the analysis. Average successive variability (ASV) was used as measure of variability. Results Among 3665 original patients, 3366 (91.8%) were included in this analysis. Median [IQR] CHA2DS2-VASc score was 3 [2–4] and HAS-BLED was 3 [2–4]. At baseline, 876 (26.0%) patients had CKD (CrCl &amp;lt;60 mL/min), with 14 (0.4%) patients having severe CKD (&amp;lt;30 mL/min), with a mean (SD) CrCl of 86.7 (47.4) mL/min. Over a mean (SD) 577.1 (122.1) days of follow-up, a total of 521 new CKD cases were found with an overall incidence of 13.1 per 100 patient-years, with 91 new severe CKD cases (1.71 per 100 patient-years). Across follow-up, prevalence of CKD and severe CKD increased progressively (both p&amp;lt;0.001) [Figure]. Mean (SD) AVS was −0.567 (±2.803) mL/min. According to AVS, patients were divided into quartiles: i) Q1: +34.012/+0.450; ii) Q2: +0.449/−0.443; iii) Q3: −0.443/−1.503; Q4: −1.505/−19.750. While no difference was found in stroke/systemic embolism, rate of major bleeding was higher in Q4 (4.5%) and Q1 (4.0%) than in other quartiles (Q2 2.5%, Q3 2.0%; p=0.009) as well as all-cause death (Q4: 6.7%; p=0.003 compared to other quartiles). A Cox multivariate adjusted model documented that AVS Q1 and Q4 were independently associated with a higher risk of major bleeding, while Q4 was associated with a higher risk of all-cause death (Table). Conclusion In a cohort of AF patients treated with warfarin, characterized by a progressive increase in the proportion with CKD and severe CKD, the largest reduction in CrCl throughout follow-up was associated to an increased risk of major bleeding and all-cause death. Renal Function Trajectories Funding Acknowledgement Type of funding source: None

Preserved peritoneal function by short-term two-day peritoneal rest in hemodialysis combination therapy patients.

Several reports have demonstrated that peritoneal rest (PR) is considered to preserve the peritoneal function in peritoneal dialysis (PD) patients. However, there has been no report that examines the peritoneal permeability before and after a short-term PR of two days. We examined the effect of the two-day PR on peritoneal permeability. We observed and compared the daily PD ultrafiltration changes in the four PD and hemodialysis (HD) combination patients from the start of dialysis therapy throughout the total observation period of each case. Next, 6months after the initiation of dialysis therapy we performed a set of peritoneal equilibrium tests (PET) before and after the 2-day PR. D/P creatinine, daily urine volume, daily ultrafiltration volume in PD, weekly residual renal creatinine clearance, and weekly PD creatinine clearance were measured. The daily PD ultrafiltration volume increased significantly after the 2-day PR, and gradually decreased over the last four days throughout the observation period in each patient. In the PET results, D/P creatinine in all patients decreased after the short-term PR, and accordingly the peritoneal ultrafiltration volume increased. However, urine volume, residual renal creatinine clearance, and peritoneal creatinine clearance did not change. The peritoneal permeability clearly decreased after the short-term PR. The repeated improvement in the PD ultrafiltration volume after the short-term PR implies that the peritoneal permeability alteration might be due to a reversible functional change in the initial dialysis period. These results suggest that a short-term PR may preserve the peritoneal function.

Abstract P014: 1,3-butanediol Induces Weight Loss But No Antihypertensive Effects In Male S.SHR(11) Rats, An Accelerated Model Of Renal Injury

The ketone body precursor 1,3-Butanediol (BD) has been reported to lower blood pressure in male Dahl Salt-sensitive rats fed a 2% NaCl diet and female S.SHR(11) rats on a 0.3% NaCl diet. Treatment in female S.SHR(11) was also associated with weight loss and suppression of renal injury. The present study tested whether BD attenuates hypertension and renal injury in male S.SHR(11) rats. The S.SHR(11) rat is a congenic strain generated from genetic modification of the Dahl S rat. Previously, we demonstrated that the S.SHR(11) rat fed a 0.3% NaCl diet exhibits earlier onset of kidney injury, a greater decline in kidney function compared to the Dahl S rat despite having similar blood pressure, thus providing a better model to test potential therapeutic interventions. Rats (7 -18 weeks old) were divided into two groups: the treatment group that received BD (20%) for 10 weeks via drinking water and controls on ad libitum water and both maintained on a low-salt rodent chow (Teklad 7034, 0.3% NaCl; n=5-6/group). Systolic blood pressure was measured after 9 weeks by tail-cuff plethysmography. After 10 weeks of BD treatment, 24h urine was collected and tissues were harvested. Treated rats were smaller than controls (330.2 ± 14.2 vs. 449.8 ± 22.9 g, p= 0.001). Urine excretion rate was lower in treated rats (11.3± 1.1 vs. 19.6 ± 3.8 ml/day, p=0.047) whereas kidney weight normalized to body weight was higher in this group (0.95 ± 0.04 vs. 0.77 ± 0.03 %, p=0.011). BD did not lower systolic blood pressure (157.0 ±14.0 vs. 163.9 ±14.6 mmHg, p=0.740). Proteinuria was diminished in the treated group, although not significant (135 ± 51 vs. 311 ± 67 mg/day, p= 0.064). Renal fibrosis (7.6 ± 0.61 vs. 9.4 ± 0.95 %, p=0.139), plasma creatinine (0.46 ±0.03 vs. 0.49 ± 0.01 mg/dL, p=0.466), and creatinine clearance normalized to kidney weight (0.57 ±0.05 vs. 0.67 ± 0.02 ml/min, p= 0.138) were not changed by treatment. Blood urea nitrogen was similar between groups (30.7 ± 2.57 vs. 27.4 ± 2.25mg/dL, p= 0.367). The current data demonstrate that BD does not mitigate hypertension nor improve renal function in male S.SHR(11) rats suggesting potential sex differences in the antihypertensive effects of BD. However, weight loss which has been associated with ketogenic interventions such as BD was still observed in this study.

Equations to Estimate the Normalized Creatinine Generation Rate (CGRn) in 3/Week Dialysis Patients With or Without Residual Kidney Function

Normalized creatinine generation rate (CGRn) can be computed for a variety of dialysis schedules using a recently described kinetic modeling program. However, the availability of estimating equations might facilitate broader study of this metric. We developed equations to estimate CGRn based on modeling and then tested them against modeled CGRn values in the Frequent Hemodialysis Network Nocturnal Trial baseline (3/week) dataset. We used a "what-if" derivation of a previously published variable volume 2-pool creatinine kinetic model to generate predicted predialysis values of serum creatinine that would result from creatinine generation rates of 250-2000mg/day in patients with creatinine distribution volumes of 20 to 50L, dialyzed from 60 to 480min per treatment three times a week. Then, in patients with residual kidney function, we calculated an "anuric expected predialysis serum creatinine value" before applying the same equations. We then compared estimated CGRn values as predicted by this approach with modeled values in patient data from the Frequent Hemodialysis Network Nocturnal Trial. The estimating equations for CGRn yielded results similar to those obtained with formal modeling, in both anuric patients and those with residual kidney function, with mean percent error of 0.845±6.15 (SD) in anuric patients, and ‒0.29±4.90 in patients with a mean creatinine clearance of 5.44±4.82mL/min, with R-squared values of 0.96 in both anuric patients and those with residual renal clearance of creatinine. In patients dialyzed 3/week, CGRn can be estimated using prediction equations. Use of these equations may facilitate broader investigation of CGRn as a measure of nutritional status and outcome.