Glepaglutide is a long-acting glucagon-like peptide (GLP)-2 analogue developed to improve intestinal absorption in patients with short bowel syndrome (SBS). The authors conducted a trial to establish the efficacy and safety of glepaglutide in reducing parenteral support (PS) needs in patients with SBS with intestinal failure.

In an international, placebo-controlled, randomized, parallel-group, double-blind, phase 3 trial, patients with SBS with intestinal failure requiring PS ≥3 d/wk were randomized 1:1:1 to 24 weeks of glepaglutide 10 mg twice weekly or once weekly or placebo. PS volume was equivalently reduced if mean urine volume of a 48-hour balance period exceeded baseline values by >10%.

One hundred six patients were randomized and dosed. Glepaglutide twice weekly significantly reduced weekly PS volumes from baseline to week 24 vs placebo (mean change, -5.13 vs -2.85 L/wk; P = .0039; primary end point). Results were similar across major anatomic subgroups. Glepaglutide twice weekly was also superior to placebo for key secondary end points of proportion of patients achieving clinical response, defined as ≥20% PS volume reduction from baseline to weeks 20 and 24 (65.7% vs 38.9%; P = .0243) and patients achieving a reduction in days on PS ≥1 d/wk from baseline to week 24 (51.4% vs 19.4%; P = .0043). Complete PS weaning ("enteral autonomy") was achieved for 5 patients (14%) receiving glepaglutide twice weekly vs 0 for patients receiving placebo. No statistically significant differences were found for glepaglutide once weekly vs placebo for primary or key secondary end points. Significant glepaglutide benefits on patient-reported outcome (Patient Global Impression of Change) were found. Glepaglutide was assessed to be safe and well tolerated.

Glepaglutide treatment in patients with SBS with intestinal failure resulted in clinically relevant reductions in PS requirements and was well tolerated. (ClinicalTrials.gov, Number: NCT03690206; ClinicalTrialsRegister.eu, Number: 2017-004394-14.).

Accurate determination of renal function is of utmost importance in chronic intestinal failure (CIF) patients on parenteral nutrition (PN) and creatinine based glomerular filtration rate (GFR) estimating equation is used in clinical practice. The aim of the present study is to evaluate the reliability of 3 CKD-EPI GFR estimating equations (eGFR) (creatinine, cystatin C or combined creatinine/cystatin C) compared with the reference method which is Iohexol plasma clearance (mGFR) in patients on long-term PN (>6 months) owing to CIF.

Forty-eight patients (25 F) with a median age of 58 years (Interquartile Range:15) presenting CIF on PN for a median duration of 93 months (75) were included in this retrospective study. Concordance studies were performed by Pearson correlation and Bland-Altman method (Mean bias-Confidence Interval). Accuracy of the formulas was estimated with P30 representing the proportion of eGFR within 30 % of mGFR (±30 %).

Median mGFR was 65 (29) ml/min/1.73 m2 and the median eGFR was 85 (43) ml/min/1.73 m2 with 2009 CKD-EPIcreatinine, 74 (47) ml/min/1.73 m2 with 2012 CKD-EPIcystatin and 75 (48) ml/min/1.73 m2 with 2012 CKD-EPIcombined Cystatin C/Creatinine based formulas. The agreements were not acceptable for clinical practice. Median bias as well as lower and upper confidence intervals were for mGFR vs. eGFR (2009 CKD-EPIcreat): +21,1 (16.7,25.3), for mGFR vs. eGFR (2012 CKD-EPIcyst): +14.4 (12.9,20.5) and for mGFR vs. eGFR (2012 CKD-EPIcomb): +9.3 (7.9,15.5). Accuracy of all formulas estimated by P30 was less than 80 %. With the 3 eGFR equations, more than 46 % of patients were poorly stratified according to the classification of chronic kidney disease (CKD) with an overall tendency towards underestimation of the disease severity. Forty-seven percent of the patients had mGFR<60 ml/min/1.73 m2 corresponding to CKD Stage III or worse.

The eGFR estimating CKD-EPI equations significantly miscalculate the true levels of renal function in patients with CIF on PN and should be used with caution in daily clinical practice.

Patients with chronic intestinal failure (CIF) are at increased risk of developing renal impairment. The aim of this study was to evaluate the occurrence of chronic kidney disease (CKD) in patients dependent on home parenteral nutrition (HPN) and assess risk factors for renal impairment, including patients with all mechanisms of CIF.

This was a cohort study of patients initiated on HPN between March 1, 2015, and March 1, 2020, at a national UK IF Reference Centre. Patients were followed from their first discharge with HPN until HPN cessation or the end of follow-up on December 31, 2021.

There were 357 patients included in the analysis. Median follow-up time was 4.7 years. At baseline, >40% of patients had renal impairment, with 15.4% fulfilling the criteria for CKD. Mean estimated glomerular filtration rate (eGFR) decreased significantly during the first year after initiation of HPN from 93.32 ml/min/1.73 m2 to 86.30 ml/min/1.73 m2 at the first year of follow-up (P = 0.002), with sequential stabilization of renal function. Increased age at HPN initiation and renal impairment at baseline were associated with decreased eGFR. By the end of follow-up, 6.7% patients developed renal calculi and 26.1% fulfilled the criteria for CKD.

This is the largest study of renal function in patients receiving long-term HPN. After the first year following HPN initiation, the rate of decline in eGFR was similar to that expected in the general population. These findings should reassure patients and clinicians that close monitoring of renal function can lead to good outcomes.

Home parenteral nutrition (HPN) prescriptions should be individualised in adults with chronic intestinal failure (IF). The aims of the review were to explore HPN requirements and available guidelines and to determine whether adults (≥ 18 years) receive recommended parenteral nutrient doses.

Online databases searches identified empirical evidence (excluding case-reports), reviews and guidelines (Published 2006-2024 in English language). Additional reference lists were hand-searched. Older studies, cited in national guidelines were highlighted to map evidence source. Two reviewers screened 1660 articles independently, with 98 full articles assessed and 78 articles included (of which 35 were clinical studies). Citation tracking identified 12 older studies.

A lack of evidence was found assessing parenteral macronutrient (amounts and ratios to meet energy needs), fluid and electrolyte requirements. For micronutrients, 20 case series reported serum levels as biomarkers of adequacy (36 individual micronutrient levels reported). Studies reported levels below (27 out of 33) and above (24 out of 26) reference ranges for single micronutrients, with associated factors explored in 11 studies. Guidelines stated recommended parenteral dosages. Twenty-four studies reported variable proportions of participants receiving HPN dosages outside of guideline recommendations. When associated factors were assessed, two studies showed nutrient variation with type of HPN administered (multichamber or individually compounded bags). Five studies considered pathophysiological IF classification, with patients with short bowel more likely to require individualised HPN and more fluid and sodium.

This review highlights substantial evidence gaps in our understanding of the parenteral nutritional requirements of adult receiving HPN. The conclusions drawn were limited by temporal bias, small samples sizes, and poor reporting of confounders and dose. Optimal HPN nutrient dose still need to be determined to aid clinical decision-making and further research should explore characteristics influencing HPN prescribing to refine dosing recommendations.

Renal impairment is a common complication in patients with short bowel syndrome with intestinal failure (SBS-IF). Glucagon-like peptide-2 analogs, such as apraglutide, have been developed as a treatment option for SBS-IF. This study assessed the potential for apraglutide overexposure in individuals with severely impaired renal function versus healthy volunteers with normal renal function. In this phase 1, open-label, multicenter, nonrandomized, parallel-group study, a single dose of apraglutide 5 mg was administered subcutaneously to individuals with severely impaired renal function (<30 mL/min/1.73 m2) and healthy volunteers with normal renal function (≥90 mL/min/1.73 m2). Primary pharmacokinetic endpoints were maximum observed concentration (Cmax) and exposure to apraglutide (area under the curve [AUC] from time 0 to infinity [AUCinf], and AUC from time 0 to the last quantifiable concentration [AUClast]). Each group comprised 8 individuals. Results show that patients with severe renal impairment do not have increased apraglutide exposure. Apraglutide achieved a lower Cmax and AUCinf in individuals with severe renal impairment versus those with normal renal function (Cmax = 36.9 vs 59.5 ng/L; AUCinf = 3100 vs 4470 h · ng/mL, respectively). The respective geometric mean ratios were 0.620 and 0.693 for Cmax and AUCinf, and the upper bound of their 90% confidence intervals were <2, indicating patients with severe renal impairment were not overexposed to apraglutide versus those with normal renal function. Adverse events were mild or moderate in severity. Apraglutide does not require dose reduction for any degree of renal impairment and could be used in a broader patient population of renally impaired patients without dose adjustment.

In 2016, ESPEN published the guideline for Chronic Intestinal Failure (CIF) in adults. An updated version of ESPEN guidelines on CIF due to benign disease in adults was devised in order to incorporate new evidence since the publication of the previous ESPEN guidelines.

The grading system of the Scottish Intercollegiate Guidelines Network (SIGN) was used to grade the literature. Recommendations were graded according to the levels of evidence available as A (strong), B (conditional), 0 (weak) and Good practice points (GPP). The recommendations of the 2016 guideline (graded using the GRADE system) which were still valid, because no studies supporting an update were retrieved, were reworded and re-graded accordingly.

The recommendations of the 2016 guideline were reviewed, particularly focusing on definitions, and new chapters were included to devise recommendations on IF centers, chronic enterocutaneous fistulas, costs of IF, caring for CIF patients during pregnancy, transition of patients from pediatric to adult centers. The new guideline consist of 149 recommendations and 16 statements which were voted for consensus by ESPEN members, online in July 2022 and at conference during the annual Congress in September 2022. The Grade of recommendation is GPP for 96 (64.4%) of the recommendations, 0 for 29 (19.5%), B for 19 (12.7%), and A for only five (3.4%). The grade of consensus is "strong consensus" for 148 (99.3%) and "consensus" for one (0.7%) recommendation. The grade of consensus for the statements is "strong consensus" for 14 (87.5%) and "consensus" for two (12.5%).

It is confirmed that CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for the underlying gastrointestinal disease and to provide HPN support. Most of the recommendations were graded as GPP, but almost all received a strong consensus.

Massive intestinal resection is a regrettably necessary but life-saving intervention for progressive or fulminant necrotizing enterocolitis (NEC). However, the resultant short bowel syndrome (SBS) poses its own array of challenges and complications. Within hours of such an abrupt loss of intestinal length, the intestine begins to adapt. Our ability to understand this process of intestinal adaptation has proven critical in our ability to clinically treat the challenging problem of short bowel syndrome. This review first highlights key data relating to intestinal adaptation including structural and functional changes, biochemical regulation, and other factors affecting the magnitude of intestinal adaptation responses. We then focus on intestinal rehabilitation as it relates to strategies to enhance intestinal adaptation while meeting nutritional needs and preventing complications of parenteral nutrition.

Attending diligently to the nutrition and hydration needs of patients with short bowel syndrome (SBS) is a key tenet of their care, both postoperatively and in the years that follow. For, without each, patients are left to themselves to navigate the nutrition consequences of SBS, including malnutrition, nutrient deficiencies, renal compromise, osteoporosis, fatigue, depression, and impaired quality of life. The intent of this review is to discuss the initial nutrition assessment, oral diet, hydration, and home nutrition support for the patient with SBS.

Intestinal failure (IF) is a complex medical condition that is caused by a constellation of disorders, resulting in the gut's inability to adequately absorb fluids and nutrients to sustain hydration, growth, and survival, thereby requiring the use of parenteral fluid and/or nutrition. Significant advancements in intestinal rehabilitation have resulted in improved survival rates for individuals with IF. There are distinct differences, however, related to etiology, adaptive potential and complications, and medical and surgical management when comparing children with adults. The purpose of this review is to contrast the similarities and differences between these two distinct groups and provide insight for future directions, as a growing population of pediatric patients will cross into the adult world for IF management.

This guideline will inform physicians, nurses, dieticians, pharmacists, caregivers and other home parenteral nutrition (HPN) providers, as well as healthcare administrators and policy makers, about appropriate and safe HPN provision. This guideline will also inform patients requiring HPN. The guideline is based on previous published guidelines and provides an update of current evidence and expert opinion; it consists of 71 recommendations that address the indications for HPN, central venous access device (CVAD) and infusion pump, infusion catheter and CVAD site care, nutritional admixtures, program monitoring and management. Meta-analyses, systematic reviews and single clinical trials based on clinical questions were searched according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing Scottish Intercollegiate Guidelines Network methodology. The guideline was commissioned and financially supported by ESPEN and members of the guideline group were selected by ESPEN.

Glepaglutide is a novel, ready-to-use, long-acting, glucagon-like peptide-2 (GLP-2) analog intended for the treatment of patients with short bowel syndrome (SBS). This study investigated the impact of renal function on the pharmacokinetics and safety of glepaglutide.

In this 3-site, non-randomized, open-label study, 16 subjects were enrolled: 4 with severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m²), 4 with end stage renal disease (ESRD) not on dialysis (eGFR < 15 mL/min/1.73 m²), and 8 matching controls with normal renal function (eGFR ≥ 90 mL/min/1.73 m²). Blood samples were collected over a 14-day period following a single subcutaneous (SC) dose of glepaglutide 10 mg. Safety and tolerability were assessed throughout the study. The primary pharmacokinetic parameters were area under the curve between dosing and 168 h (AUC_0-168 h) and the maximum plasma concentration (C_max).

There was no clinically relevant difference between subjects with severe renal impairment/ESRD and normal renal function with respect to total exposure (AUC_0-168 h) and peak plasma concentrations (C_max) of glepaglutide following a single SC dose. A single SC dose of glepaglutide 10 mg appeared safe and well tolerated in subjects with normal renal function and subjects with severe renal impairment or ESRD. No serious adverse events were reported, and no safety issues were identified.

No difference in glepaglutide pharmacokinetics was seen between renal impaired and normal subjects. Based on this trial, dose adjustment appears not to be warranted in SBS patients with renal impairment.

The trial is registered at http://www.

gov (NCT04178447) and has the EudraCT number: 2019-001466-15.

The development of intestinal failure-related complications in Finnish adults is unknown. This study aimed to investigate the incidence of catheter-related bloodstream infections (CRBSI), and the longitudinal changes in biochemical liver and kidney tests in a nationwide cohort.

The search for Finnish adults with intestinal failure (IF) utilized a survey to Finnish health-care providers (n = 111) with the potential to provide long-term parenteral support (PS) for adult IF. Our nationwide, cross-sectional cohort included all IF patients aged ≥ 18 years who had received PS for ≥ 120 d in 2017. Data regarding CRBSI and biochemical liver and kidney tests were collected from patient records at the start of PS up to the latest available measurement in 2017.

In the nationwide cohort of 52 patients, the CRBSI incidence was 1.35/1000 catheter days. Seventy-three percent of CRBSI in a long-term catheter led to catheter replacement. During a median PS duration of 27.5 (interquartile range [IQR] 11.3-57.3) months, a statistically significant median change occurred in estimated glomerular filtration rate (eGFR; -8.5 ml/min/1.73 m², IQR -30-7, p = .005) and alkaline phosphatase (ALP; 26 U/l, IQR -11-95, p = .019). In a multiple regression model for eGFR at data collection, baseline eGFR and age were strong explanatory variables.

Incidence of CRBSI, but not treatment strategies, in this nationwide adult IF population correspond well to those reported from specialized centers. Decreased kidney function and abnormal liver test results are frequent findings, and even more so over time, emphasizing the importance of regular monitoring.

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960's, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.

Intestinal failure (IF) secondary to short bowel syndrome is a challenging and complex medical condition with significant risk for surgical and medical complications. Significant advancements in the care of this patient population have led to improved survival rates. Due to their intensive medical needs children with IF are at risk for long-term complications that require comprehensive management and close monitoring. The purpose of this paper is to review the available literature emphasizing the surgical aspects of care for children with IF secondary to short bowel syndrome. A key priority in the surgical care of this patient population includes strategies to preserve available bowel and maximize its function. Utilization of novel surgical techniques and autologous bowel reconstruction can have a significant impact on children with IF secondary to short bowel syndrome related to the function of their bowel and ability to achieve enteral autonomy. It is also important to understand the potential long-term complications to ensure strategies are put in place to mitigate risk with early detection to improve long-term outcomes.

Long-term parenteral nutrition (PN) has been associated with renal complications, including hypercalciuria, nephrocalcinosis, proteinuria and reduced glomerular filtration rate (GFR). Pediatric data are scarce and mostly short-term. Our study aimed to evaluate renal complications in children with intestinal failure (IF) receiving long-term PN.

A cross-sectional study was performed in a tertiary pediatric IF clinic of patients receiving home-PN treatment for more than 1 year. Data regarding medical background, anthropometrics, laboratory investigations and abdominal sonography were retrieved.

Complete data were available for 15 children (67% males), with a median age of 6 (range 1.5-15) years and a median (IQR) PN duration of 4 (1.5-6) years. Low-grade proteinuria was identified in 61% and microalbuminuria in 30% of the cohort. Hypercalciuria and hyperoxaluria were present in 50% and 46%, respectively. One patient had nephrocalcinosis. The estimated GFR was normal in all but one patient who had pre-existing kidney disease.

Pediatric IF patients can present with preserved kidney function after years of PN treatment. Despite the high prevalence of hypercalciuria, nephrocalcinosis was not common. Base line and long-term monitoring of various aspects of renal function would be essential to characterize the effects of prolonged PN on kidney functions in pediatric patients.

Chronic intestinal failure (CIF) is a rare but feared complication of Crohn's disease. Depending on the remaining length of the small intestine, the affected intestinal segment, and the residual bowel function, CIF can result in a wide spectrum of symptoms, from single micronutrient malabsorption to complete intestinal failure. Management of CIF has improved significantly in recent years. Advances in home-based parenteral nutrition, in particular, have translated into increased survival and improved quality of life. Nevertheless, 60% of patients are permanently reliant on parenteral nutrition. Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy. The outcomes of patients with CIF could be greatly improved by more effective prevention, understanding, and treatment. In complex cases, the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation, nutritional support, and an improved quality of life. Here, we summarize current literature on CIF and short bowel syndrome, encompassing epidemiology, pathophysiology, and advances in surgical and medical management, and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.

Progressive renal impairment, given by an annual decline in estimated glomerular filtration rate (eGFR), has been described in patients with intestinal failure (IF) receiving home parenteral support (HPS). The objective of this study was to examine changes in eGFR over 5 years following initiation of HPS treatment and to identify potential risk factors for loss of renal function.

This retrospective database study investigates eGFR changes in nonmalignant IF patients discharged with HPS from Rigshospitalet, Copenhagen, in an 8-year period.

One year after HPS initiation, mean eGFR decreased by 15.3 ml/min/1.73 m² . Paired t-test showed a decline of 15.0 ml/min/1.73 m² (95% CI, -18.3 to -11.6; P < .0001). Over the following years, eGFR continued to decrease but at insignificant lower rates. Decreased eGFR was associated with increasing age, female sex, increasing body weight, diabetes at HPS initiation, and a high requirement of HPS volume.

In nonmalignant IF patients, the decrease of eGFR was mainly seen during the first year of HPS. This may be due to a higher risk of dehydration and possibly secondary hyperaldosteronism leading to renal damage following the onset of IF. However, the decrease in eGFR may also represent a higher production of creatinine due to a beneficial increase of muscle mass in the initial recovery phase. In general, once the patients were stabilized, the eGFR decline followed a physiological course resembling the background population. Patients with diabetes or high HPS volume needs seem to be more vulnerable and may require special attention.

The home parenteral nutrition (HPN) population face many challenges, especially with respect to fluid balance management. A low urinary sodium concentration of <20 mmol/L is commonly used as an indicator of dehydration that requires clinical assessment in these patients. The Quantab titrator dipstick measures chloride concentration of a solution and correlates with sodium concentration. We assessed whether it would be feasible to use the Quantab dipstick in the HPN population and explored relationships between Quantab dipstick estimated chloride concentration and quality of life (QOL).

Patients on HPN were asked to collect urine samples at 5 specific times points (day 0,7,14, 21 and 28) to send to the laboratory for formal electrolyte analysis. The participant and a member of laboratory staff tested these samples with the Quantab dipstick to estimate urinary chloride concentration. Participants were instructed to complete a QOL questionnaire at each of the 5 time-points in addition to a baseline demographic questionnaire and an end-of-study questionnaire. Six participants completed an interview at the end of the study period. The relationship between participant-derived and laboratory-derived data was assessed using rank correlation coefficients. QOL assessment was correlated with urine dipstick measurements.

10 patients on HPN completed the study. Data on chloride concentration as estimated by the dipstick (assessed by participants and by the laboratory) and sodium concentration from the laboratory were available for 47 urine samples. There was a positive relationship between participant dipstick estimated chloride concentration and laboratory sodium (Kendall's τ = 0.45; P < 0.001; Spearman's r_s = 0.58 P < 0.001; 47 pairs). There was a strong correlation between chloride concentrations estimated by dipstick in the laboratory and by participants (Kendall 0.58 p < 0.001, Spearman's 0.69 p < 0.001; 47 pairs). In exploratory analyses, there was no relationship between QOL and dipstick estimated chloride concentration. Participants had no issues collecting urine samples but some difficulties were reported with determining the dipstick reading.

Patients on HPN are able to collect urine specimens, complete QOL questionnaires, and are capable of using the Quantab dipstick to estimate urinary chloride concentration. The Quantab dipstick correlates with laboratory measured sodium and chloride concentrations. Further work is required to fully establish whether this point-of-care test could be used to guide fluid balance management in the HPN population.

Renal dysfunction can complicate home parenteral nutrition (HPN). The aims were, in the context of pediatric HPN, to assess renal function using the measured glomerular filtration rate (mGFR), determine the most accurate formula(s) to estimate GFR, and identify possible underlying mechanisms of renal impairment.

A retrospective study was performed in 2 centers. Patients receiving HPN and aged 2-16 years without medical history of nephropathy were included. GFR was measured using iohexol clearance. Estimated GFR (eGFR) was calculated using creatinine, cystatin C-based, and combined (eGFR_cr+cyst ) Schwartz formulas.

A total of 36 patients (18 females) were included; they received HPN for 8 (2-16) years. The primary digestive disease was short-bowel syndrome for 16 (44%) patients, gastrointestinal motility disorder for 10 (28%), or congenital diarrhea for 10 (28%). The median (range) mGFR was 99 (33-136) ml/min/1.73 m² ; 9 (25%) patients had mildly decreased mGFR (<90 and ≥60 ml/min/1.73 m² ), and 2 (6%) had mildly to severely decreased mGFR (<60 ml/min/1.73 m² ). The eGFR_cr+cyst formula was the most accurate and precise to estimate GFR. A significant negative correlation between mGFR and PN duration was found for patients receiving PN for 6-7/7 days (P = .008). Activation of the renin-angiotensin system was identified in 15 of 36 (42%) patients.

Renal dysfunction was frequent and correlated with the duration of PN only for patients with the most severe intestinal failure. The use of eGFR_cr+cyst improves its detection in these patients. Chronic dehydration may be an underlying mechanism.

Kidney disease is a frequent but underestimated complication in patients suffering from intestinal failure (IF) treated by long-term home parenteral nutrition (HPN). The evolution in glomerular filtration rate (GFR) over time is poorly characterized. The current equations for estimating GFR have limited precision. No study has specifically investigated the reliability of recent creatinine-based estimated GFR (eGFR) equations in this population. The aim of this study was to evaluate the renal function decline under home parenteral nutrition (HPN) with a gold standard method and compare the performances of routinely used eGFR equations.

Forty patients with HPN and two or more GFR measurements were retrospectively studied. The renal function decline was calculated by the slope drawn between the successive measured GFRs (mGFRs). The performances of the Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, full age spectrum and revised Lund-Malmö equations were compared with reference methods (inulin or iohexol clearance).

The mean mGFR was 78 ± 28 mL/min/1.73 m2. The annual decline of mGFR was -1.9 mL/min/1.73 m2/year. No predisposing factor was identified to predict impairment in renal function. eGFR formulas grossly overestimated mGFR and had a low level of accuracy.

Patients with IF are at significant risk for impaired renal function. In this population, the tested eGFR equations were inaccurate. However, monitoring kidney function with mGFR remains important in these patients, as their GFR regularly declines and no specific risk factor has yet been identified.

Renal impairment is a common complication in patients with intestinal failure that is mostly caused by short bowel syndrome (SBS) and is associated with adverse outcomes that severely affect the quality of life or even survival. The prevalence and risk factors for renal impairment in patients with SBS remain unclarified. Therefore, we aimed to determine the prevalence of renal impairment and identify potential risk factors for renal impairment in adult patients with SBS. We retrospectively identified 199 patients diagnosed with SBS admitted to the Department of General Surgery between January 1, 2012 and January 1, 2019, from a prospectively maintained database. Overall, 56 patients (28.1%) with decreased renal function (eGFR < 90 mL/min/1.73 m²). The median duration of SBS was 7 months (IQR, 3-31 months) and the mean eGFR was 103.1 ± 39.4 mL/min/1.73 m². Logistic regression modeling indicated that older age [odds ratio (OR), 1.074; 95% CI, 1.037-1.112, P < 0.001], kidney stones (OR, 4.887; 95% CI, 1.753-13.626; P = 0.002), decreased length of the small intestine (OR, 0.988; 95% CI, 0.979-0.998; P = 0.019), and prolonged duration of SBS (OR, 1.007; 95% CI, 1.001-1.013; P = 0.046) were significant risk factors for renal impairment. This is the largest study that has specifically explored the risk factors for renal impairment in a large cohort of adults with SBS. The present study showed that renal function should be closely monitored during treatment, and patients should be given prophylactic interventions if necessary. This retrospective study is a part of clinical study NCT03277014, registered in ClinicalTrials.gov PRS. And the PRS URL is http://register.clinicaltrials.gov.

Outcomes of pediatric intestinal failure (PIF) have improved recently, with other comorbidities, such as increased echogenicity/nephrocalcinosis on ultrasound (US) in long-term survivors now evident. We evaluated the significance of nephrocalcinosis over time in PIF and its impact on renal function.

Retrospective analysis on a cohort of PIF patients was performed. Presence of nephrocalcinosis and/or increased renal echogenicity (identified on US), estimated glomerular filtration rate (eGFR; ml · min · 1.73 m2), renal tubular function, PN volume (ml · kg · day) and PN exposure time (hours/day) were reviewed annually over a follow-up period of 2 years. Outcomes in the nephrocalcinosis versus normal US groups were compared.

Forty patients (28 boys, median age 2.7 years) were followed for 2 years. Fifteen (38%) had either increased echogenicity or nephrocalcinosis (group 1) at initial US. US were normal in the remaining 25 (62%) on initial assessment (group 2). eGFR did not differ between group 1 and group 2 at baseline (118 vs 133, P = 0.51) and year 2 (130 vs 131, P = 1.00). The percentage of patients with abnormal markers of tubular function was similar in both groups at year 2 (high urine calcium: creatinine 33 versus 30, P = 0.83; high urine calcium: citrate 39 versus 42, P = 0.87; low urine citrate: creatinine 15 versus 17, P = 1.00; high urine oxalate: creatinine 39 versus 25, P = 0.77).

A large proportion of PIF patients with a history of parenteral nutrition (PN) exposure have nephrocalcinosis and/or increased echogenicity on US. Over a 2-year follow-up period, however, these abnormalities had no impact on eGFR or renal tubular function.

This guideline will inform physicians, nurses, dieticians, pharmacists, caregivers and other home parenteral nutrition (HPN) providers, as well as healthcare administrators and policy makers, about appropriate and safe HPN provision. This guideline will also inform patients requiring HPN. The guideline is based on previous published guidelines and provides an update of current evidence and expert opinion; it consists of 71 recommendations that address the indications for HPN, central venous access device (CVAD) and infusion pump, infusion line and CVAD site care, nutritional admixtures, program monitoring and management. Meta-analyses, systematic reviews and single clinical trials based on clinical questions were searched according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing Scottish Intercollegiate Guidelines Network methodology. The guideline was commissioned and financially supported by ESPEN and members of the guideline group were selected by ESPEN.

Renal dysfunction more frequently occurs after intestinal transplantation (ITx) than after heart, lung, or liver transplantation. We provide a clinical analysis of renal function after adult ITx.

We retrospectively analyzed 8 adult ITx patients who survived for at least 6 months between 2004 and 2018. Glomerular filtration rate (GFR) measurements were performed at baseline, at 3 and 6 months post-transplantation, and yearly. The median follow-up duration was 53.5 months.

All cases were isolated ITx; 3 received living-donor ITx, and 5 received deceased-donor ITx. The mean baseline GFR was 97 mL/min/1.73 m². The GFR had decreased by more than 50% of baseline at 1 year post-transplant. Renal dysfunction was observed in 4 patients. Two patients developed acute kidney injury due to acute rejection and sepsis. One of these patients fully recovered renal function, but the second patient died. Another 2 patients developed chronic kidney disease and required hemodialysis (HD) within 6 and 3 years, respectively. The first living-donor ITx patient lost renal function progressively over 6 years after ITx. She received a renal graft from the same living donor as for the ITx after 3 years of HD. The other patient (deceased-donor ITx) received a kidney from his daughter at 5 months after HD.

To obtain an accurate assessment of renal function, frequent direct measurements of GFR should be performed to facilitate early diagnosis of renal impairment and to determine subsequent strategies to improve renal function after ITx.

Pediatric intestinal failure (IF) is a rare and complex condition associated with significant morbidity and mortality. It is defined as the reduction of gut mass or function below the minimal needed for absorption of nutrients and fluid to sustain life and growth. Since the advent of specialized multidisciplinary intestinal rehabilitation centers, IF management has considerably evolved in the last years, but serious complications of long-term parenteral nutrition (PN) can occur. Main complications include intestinal failure-associated liver disease, growth failure, body composition imbalance, central venous access complications, micronutrient deficiencies and toxicities, metabolic bone disease, small intestinal bacterial overgrowth, and renal disease. With improvement in survival rates of patients over the last 20 years, emphasis should be on limiting IF-related comorbidities and improving quality of life. Close monitoring is pivotal to ensuring quality of care of these patients. The care of children with chronic IF should involve a comprehensive monitoring plan with flexibility for individualization according to specific patient needs. Monitoring of children on long-term PN varies significantly across units and is mainly based on experience, although few guidelines exist. This narrative review summarizes the current knowledge and practices related to monitoring of children with IF. The authors also share their 20-year experience at the Royal Children's Hospital in Melbourne Australia on this topic.

Patients with short bowel syndrome might have impaired postprandial endogenous glucagon-like peptide-2 (GLP-2) secretion, which is required for optimal intestinal adaptation. We aimed to assess the therapeutic potential of glepaglutide, a novel long-acting GLP-2 analogue, for reducing faecal output and increasing intestinal absorption in patients with short bowel syndrome.

In this single-centre, double-blind, crossover, randomised phase 2 trial, adults (aged ≥18 to ≤90 years) with short bowel syndrome and with a faecal wet weight output of 1500 g/day or more were randomly assigned to receive one of six dose sequences of glepaglutide (10 mg, 1 mg; 10 mg, 0·1 mg; 1 mg, 10 mg; 1 mg, 0·1 mg; 0·1 mg, 10 mg; or 0·1 mg, 1 mg). Patients received daily subcutaneous injections of the first assigned dose of glepaglutide for 3 weeks, followed by a washout period of 4-8 weeks, and then the second dose of glepaglutide for 3 weeks. An unmasked statistician generated the randomisation list, and the trial investigator enrolled patients and assigned them their patient numbers. Trial investigators, patients, and other care providers were masked throughout the trial. The primary endpoint was the absolute change from baseline in faecal wet weight output, measured separately over the two treatment periods. Metabolic balance studies were done before and after each treatment period to assess the primary endpoint. Per-protocol analysis was used to assess the efficacy. Safety analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02690025, and has completed.

Of the 22 patients screened between Feb 5, 2016, and Jan 25, 2017, 18 patients were randomly assigned and treated with glepaglutide; 16 patients completed the trial. Treatment with 1 mg and 10 mg glepaglutide changed the adjusted mean faecal output by -592 g/day (95% CI -913 to -272; p=0·002) and -833 g/day (-1152 to -515; p=0·0002) from baseline, respectively. No changes were observed with 0·1 mg glepaglutide. Of the 18 patients who were randomly assigned to treatment, common treatment-related adverse events were stoma complications (13 [72%] patients), injection site reactions (11 [61%]), peripheral oedema (ten [56%]), nausea and abdominal pain (eight [44%] each), polyuria and fatigue (six [33%] each), abdominal distention, vomiting, and dizziness (five [28%] each); and cough and decreased appetite (four [22%] each). Related or possibly related serious adverse events were reported in two patients in the 0·1 mg dose group and two patients in the 10 mg dose group. These events included abdominal pain, stoma obstruction, catheter-related sepsis, and infection of unknown origin. No patients died during the trial.

Glepaglutide was well tolerated, and was associated with improved intestinal absorption in patients with short bowel syndrome with 1 mg and 10 mg glepaglutide, but not with 0·1 mg glepaglutide. Larger phase 3 clinical trials of longer durations have been initiated to fully assess the safety and efficacy of glepaglutide.

Zealand Pharma.

Objectives: To assess renal function in pediatric intestinal failure (IF) patients on long term home parenteral nutrition (HPN). Methods: Children who received HPN for a minimum of 3 years between 2007 and 2017 were identified from the IF clinic of a large tertiary referral center. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula at discharge on HPN, after 6 months, 1, 2, and 3 years. Results: Twenty five patients (40% male) fulfilled the inclusion criteria. The indications for HPN were due to an underlying motility disorder in 56% (14/25), enteropathy in 24% (6/25), and short bowel syndrome in 20% (5/25). At the start of HPN 80% (20/25) had a normal eGFR. Four children (17%) had an abnormal eGFR. In the group of patients with normal eGFR at the start of HPN 30% (6/20) had at least one episode of decreased eGFR in the following 3 years, however there was no significant decline in eGFR at the end of the 3 year study period. Overall there was no statistically significant deterioration of eGFR in the study population (p = 0.7898). Conclusion: In our cohort of children on long term HPN no significant decline of eGFR could be demonstrated within 3 years of starting PN.

Long-term home parenteral nutrition (LTPN) in children with chronic intestinal failure (CIF) is associated with renal complications such as fluid and electrolyte imbalances, nephrocalcinosis, nephrolithiasis, and chronic kidney disease (CKD). The etiology of CIF-associated nephropathy is multifactorial. The aim of this study was to evaluate renal involvement under LTPN. In this study, 50 patients with CIF, median age 4.2 years (1.4-9.3; 23 girls) were included. Kidney involvement was a frequent finding in this study. CKD was present in 30% of patients without correlation with LTPN duration. Glomerular proteinuria was found in the majority of patients (76%), an important long-term risk factor for the progression of CKD. Increased urinary α-1 microglobulin was significantly associated with duration (years) of LTPN and was increased in patients with CKD.

Severe short bowel syndrome (SBS) is a major cause of chronic (Type 3) intestinal failure (IF) where structural and functional changes contribute to malabsorption and risk of micronutrient deficiencies. Chronic IF may be reversible, depending on anatomy and intestinal adaptation, but most patients require long-term nutritional support, generally in the form of parenteral nutrition (PN). SBS management begins with dietary changes and pharmacologic therapies taking into account individual anatomy and physiology, but these are rarely sufficient to avoid PN. New hormonal therapies targeting intestinal adaptation hold promise. Surgical options for SBS including intestinal transplant are available, but have significant limitations. Home PN (HPN) is therefore the mainstay of treatment for severe SBS. HPN involves chronic administration of macronutrients, micronutrients, fluid, and electrolytes via central venous access in the patient's home. HPN requires careful clinical and biochemical monitoring. Main complications of HPN are related to venous access (infection, thrombosis) and metabolic complications including intestinal failure associated liver disease (IFALD). Although HPN significantly impacts quality of life, outcomes are generally good and survival is mostly determined by the underlying disease. As chronic intestinal failure is a rare disease, registries are a promising strategy for studying HPN patients to improve outcomes.

Patients who cannot ingest adequate calories to maintain body weight via their gastrointestinal tract may require parenteral nutrition (PN) at home. As with any therapy, the patient must be evaluated to determine if the home PN (HPN) is effective and the patient is free of complications. This review discusses specific items to monitor for HPN patients. Parameters to monitor can be divided into those used to determine effectiveness and those used to prevent complications of HPN. In addition, potential HPN-associated complications can be divided into those that occur with short- or long-term PN administration. Specific items to monitor are discussed within this framework.

Outcomes of children with intestinal failure have improved over the last decade. However, with improved survival, other co-morbidities have become evident. The goal of our study was to evaluate the presence of renal nephrocalcinosis or increased echogenicity in a cohort of patients with pediatric intestinal failure (PIF).

A cross-sectional prevalence design was performed in PIF patients followed by our intestinal rehabilitation program between 2013 and 2014. Renal function was evaluated using serum creatinine and urea, urine oxalate, creatinine, calcium, and calcium/creatinine ratios. Renal ultrasounds were performed to assess for echogenicity. Data was collected on intestinal failure related factors and nutritional intake. Data was analyzed using medians and Mann-Whitney U or proportions and chi square.

Fifty-four patients (median age 48months; 33 males (61%) were studied. Twenty-two patients (41%) had increased echogenicity or nephrocalcinosis on ultrasound. There were no differences in serum Creatinine or urea, but patients with nephrocalcinosis had statistically different calcium:creatinine ratio (1.69 vs 0.74; p=0.043), urine oxalate (108 vs 219; p=0.06), and serum phosphate (1.55 vs 1.75; p=0.044). Patients with echogenicity had a shorter colonic remnant (25cm vs 31cm; p=0.01), a history of longer PN exposure (928 vs 483days; p=0.05), percent PN calories (37 vs 0; p=0.05), PN h/day (13 vs 0; p=0.05), but no difference in PN Ca/phosphate/magnesium content (mmol/kg).

A large proportion of PIF patients have increased echogenicity/nephrocalcinosis on ultrasound that is associated with prolonged PN exposure. This has implications for long-term management. Regular surveillance is required, and further study is warranted to determine specific risk factors.

The European Society for Clinical Nutrition and Metabolism defined intestinal failure (IF) as "the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth". IF is classified as type 1-acute, type 2-prolonged acute and type 3-chronic IF. A short bowel syndrome (SBS) due to the intestinal malabsorption associated with a functional small intestine length of less than 200 cm is the most frequent mechanism of IF. SBS is a difficult and multifaced disease. Complications due to SBS itself and to treatments, such as long term home parenteral nutrition, can adversely affect the patient outcome. The care of SBS requires complex technologies and multidisciplinary and multiprofessional activity and expertise. Patient outcome is strongly dependent on care and support from an expert specialist team. This paper focuses on the aspects of the pathophysiology and on the complications of SBS, which are most relevant in the clinical practice, such as intestinal failure associated liver disease, renal failure, biliary and renal stones, dehydration and electrolyte depletion, magnesium deficiency and D-lactic acidosis.

Chronic Intestinal Failure (CIF) is the long-lasting reduction of gut function, below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth. CIF is the rarest organ failure. Home parenteral nutrition (HPN) is the primary treatment for CIF. No guidelines (GLs) have been developed that address the global management of CIF. These GLs have been devised to generate comprehensive recommendations for safe and effective management of adult patients with CIF.

The GLs were developed by the Home Artificial Nutrition & Chronic Intestinal Failure Special Interest Group of ESPEN. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds, and accepted in an online survey of ESPEN members.

The following topics were addressed: management of HPN; parenteral nutrition formulation; intestinal rehabilitation, medical therapies, and non-transplant surgery, for short bowel syndrome, chronic intestinal pseudo-obstruction, and radiation enteritis; intestinal transplantation; prevention/treatment of CVC-related infection, CVC-related occlusion/thrombosis; intestinal failure-associated liver disease, gallbladder sludge and stones, renal failure and metabolic bone disease. Literature search provided 623 full papers. Only 12% were controlled studies or meta-analyses. A total of 112 recommendations are given: grade of evidence, very low for 51%, low for 39%, moderate for 8%, and high for 2%; strength of recommendation: strong for 63%, weak for 37%.

CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for both the underlying gastrointestinal disease and to provide HPN support. The rarity of the condition impairs the development of RCTs. As a consequence, most of the recommendations have a low or very low grade of evidence. However, two-thirds of the recommendations are considered strong. Specialized management and organization underpin these recommendations.

The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 teduglutide studies, and pilot studies employing GLP-1 and agonists for this orphan condition.

In a 3-week, phase 2, metabolic balance study, teduglutide increased the intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 Kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Adverse events were mainly of gastrointestinal origin and consistent with the known mechanism of action of teduglutide. Pilot studies suggest that GLP-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2.

Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation in these severely disabled short-bowel syndrome patients.

Parenteral nutrition (PN) can be described as the "Intravenous administration of nutrients necessary to sustain life in those who would otherwise have died or suffered serious disease". PN is indicated in children who cannot be fully fed by the oral or intestinal route, usually as a result of intestinal failure. Intradialytic parenteral nutrition (IDPN) is rarely indicated in children on dialysis and does not confer a benefit over enteral supplements in the compliant patient with adequate intestinal function. Renal and metabolic consequences of PN are potentially life-threatening and include disorders of glucose homeostasis, acid-base and fluid and electrolyte disturbances, nephrolithiasis, impaired renal function and metabolic bone disease. Many of these complications are avoidable. Adequate clinical and biochemical assessment and monitoring of children receiving PN by a multidisciplinary nutrition support team is recommended to mitigate against the risks of these complications.

Subjects with short bowel syndrome (SBS) have impaired quality of life (QoL). No disease-specific instrument has been available to measure treatment-induced changes in QoL over time. Therefore, the aim was to develop and validate an SBS-specific QoL scale.

Classical test theory and Food and Drug Administration (FDA) guidance were applied for development and validation of the SBS-QoL™. Procedures included item generation and raw scale construction. Factor analysis, construct validity and internal consistency were assessed in a non-interventional observation, test re-test reliability and responsiveness in a randomised clinical study.

The SBS-QoL™ comprises 17 items including two subscales. Subjects assessed the scale as easy to handle and comprehensible. Good construct validity was shown by comparison with the Home Parenteral Nutrition-Quality Of Life questionnaire as an external scale, which yielded moderately high correlation (r ≥ 0.7). High internal consistency was demonstrated (Cronbach's alpha: 0.94). Also the test re-test reliability was high (r ≥ 0.95), indicating reliable reproducibility of results. The Responsiveness Index (1.84) indicated the ability of the scale to detect changes in QoL over time.

The SBS-QoL™ is an easy to handle and comprehensible SBS-specific subject-reported QoL scale. It is valid, reliable and sensitive with excellent psychometric characteristics to measure treatment-induced changes in QoL over time in subjects with SBS.