Daytime sleepiness, also known as hypersomnolence, is common among patients receiving maintenance dialysis and following successful kidney transplantation. Sleepiness may be secondary to medical comorbid conditions, medication side effect, insufficient sleep syndrome, and sleep-disordered breathing or the result of a primary central disorder of hypersomnolence, such as narcolepsy. Unrecognized and untreated sleep disorders are associated with substantial morbidity and mortality among patients with end-stage kidney disease. Effective management of hypersomnolence can improve quality of life in patients with kidney disease. This review focuses on the principal causes of sleepiness in patients with end-stage kidney disease. Awareness of these disorders by treating nephrologists is crucial. This review provides a systematic approach to guide providers through the recognition, early diagnosis, and treatment of hypersomnolence, which is commonly encountered in this patient population. Areas of future research are also suggested.

The intensive care unit (ICU) is a common source of high-acuity nephrology consultations. Although advanced chronic kidney disease is associated with increased ICU mortality, the prognosis of acute kidney injury (AKI) requiring renal replacement therapy is far worse, with short-term mortality rates that often exceed 50%. As such, it is essential that practicing nephrologists be comfortable caring for critically ill patients. This Core Curriculum article emphasizes the developments of the last decade since the last Core Curriculum installment on this topic in 2009. We focus on some of the most common causes of AKI in the critical care setting and use these AKI causes to delve into specific topics most relevant to critical care nephrology, including acute respiratory distress syndrome, extracorporeal membrane oxygenation, evolving concepts in fluid management, and shock. We conclude by reviewing the basics of palliative care nephrology and dialysis decision making in the ICU.

The multifaceted Notch signaling pathway appears to tame the autoimmune response and protect lupus-prone mice from inflammation and damage.

Potassium channels are important to control membrane potential and drive epithelial transport processes. In this issue of Kidney International, Bignon et al. report the role of the Kir4.2 K+-channel, localized at the basolateral membrane of proximal tubules, in the reabsorption of bicarbonate and the modulation of renal ammoniagenesis. The findings have implications for our understanding of how the kidney reacts to hypokalemia, an acid load, and the metabolic acidosis of patients with advanced stages of chronic kidney disease.

Insulin has many varied actions in the proximal tubule. Two distinct activities include upregulation of sodium/bicarbonate reabsorption and downregulation of gluconeogenesis. The inability to perform these 2 tasks simultaneously under fed and fasted conditions can lead to hyper- or hypoglycemia, acidosis, and/or impaired extracellular fluid regulation. Nakamura and colleagues illuminate our understanding of this process, which appears to be managed in part by recruitment of different insulin receptor substrates under different physiological conditions.

Chronic interstitial nephritis in agricultural communities (CINAC) is a progressive form of tubulointerstitial nephritis affecting agricultural workers in different parts of the world. Its underlying etiology is not known, although a study by Vervaet and coworkers in this issue of Kidney International provides strong evidence that CINAC is a lysosomal tubulopathy induced by toxin exposure. Key to this important discovery is a thorough morphologic analysis of kidney tissue, including ultrastructural as well as histopathologic examination.

Mosaicism is defined as the presence of 2 genetically different populations of cells in a single organism, resulting from a mutation during early embryogenesis. Hopp et al. characterized mosaicism in 20 unresolved ADPKD families, using next-generation sequencing techniques with DNA isolated from blood cells. Mosaicism may be involved in 1% of ADPKD families, and it may explain some atypical disease phenotypes.

Much of medical data is buried in the free text of clinical notes and not captured by structured data, such as administrative codes. Natural language processing (NLP) can locate and use information that resides in unstructured free text. Chan et al. demonstrate that NLP is sensitive for identifying symptoms in hemodialysis patients. These findings highlight the benefit NLP may bring to nephrology and should prompt discussion of important considerations for NLP system design and implementation.

Rationale & Objective Cytokine release syndrome is a well-known complication of chimeric antigen receptor T-cell (CAR-T) therapy and can lead to multiorgan dysfunction. However, the nephrotoxicity of CAR-T therapy is unknown. We aimed to characterize the occurrence, cause, and outcomes of acute kidney injury (AKI), along with the occurrence of electrolyte abnormalities, among adults with diffuse large B-cell lymphoma receiving CAR-T therapy. Study Design Case series. Setting & Participants We reviewed the course of 78 adults receiving CAR-T therapy with axicabtagene ciloleucel or tisagenlecleucel at 2 major cancer centers between October 2017 and February 2019. Baseline demographics, comorbid conditions, medications, and laboratory values were obtained from electronic health records. AKI was defined using KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The cause, clinical course, and outcome of AKI events and electrolyte abnormalities in the first 30 days after CAR-T infusion were characterized using data contained in electronic health records. Results Among 78 patients receiving CAR-T therapy, cytokine release syndrome occurred in 85%, of whom 62% were treated with tocilizumab. AKI occurred in 15 patients (19%): 8 had decreased kidney perfusion, 6 developed acute tubular necrosis, and 1 patient had urinary obstruction related to disease progression. Those with acute tubular necrosis and obstruction had the longest lengths of stay and highest 60-day mortality. Electrolyte abnormalities were common; hypophosphatemia, hypokalemia, and hyponatremia occurred in 75%, 56%, and 51% of patients, respectively. Limitations Small sample size; AKI adjudicated by retrospective chart review; lack of biopsy data. Conclusions In this case series of patients with diffuse large B-cell lymphoma receiving CAR-T therapy, AKI and electrolyte abnormalities occurred commonly in the context of cytokine release syndrome.

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology–Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD.

Rationale & Objective Patients with chronic kidney disease (CKD) are particularly sensitive to dietary sodium. We evaluated a self-management approach for dietary sodium restriction in patients with CKD. Study Design Randomized controlled trial. Setting & Participants Nephrology outpatient clinics in 4 Dutch hospitals. 99 adults with CKD stages 1 to 4 or a functioning (estimated glomerular filtration rate ≥ 25 mL/min/1.73 m2) kidney transplant, hypertension, and sodium intake >130 mmol/d. Intervention Routine care was compared with routine care plus a web-based self-management intervention including individual e-coaching and group meetings implemented over a 3-month intervention period, followed by e-coaching over a 6-month maintenance period. Outcomes Primary outcomes were sodium excretion after the 3-month intervention and after the 6-month maintenance period. Secondary outcomes were blood pressure, proteinuria, costs, quality of life, self-management skills, and barriers and facilitators for implementation. Results Baseline estimated glomerular filtration rate was 55.0 ± 22.0 mL/min/1.73 m2. During the intervention period, sodium excretion decreased in the intervention group from 188 ± 8 (SE) to 148 ± 8 mmol/d (P < 0.001), but did not change significantly in the control group. At 3 months, mean sodium excretion was 24.8 (95% CI, 0.1-49.6) mmol/d lower in the intervention group (P = 0.049). At 3 months, systolic blood pressure (SBP) decreased in the intervention group from 140 ± 3 to 132 ± 3 mm Hg (P < 0.001), but was unchanged in the control group. Mean difference in SBP across groups was −4.7 (95% CI, −10.7 to 1.3) mm Hg (P = 0.1). During the maintenance phase, sodium excretion increased in the intervention group, but remained lower than at baseline at 160 ± 8 mmol/d (P = 0.01), while it decreased in the control group from 174 ± 9 at the end of the intervention period to 154 ± 9 mmol/d (P = 0.001). Consequently, no difference in sodium excretion between groups was observed after the maintenance phase. There was no difference in SBP between groups after the maintenance phase. Limitations Limited power, postrandomization loss to follow-up, Hawthorne effect, lack of dietary data, short-term follow-up. Conclusions A coaching intervention reduced sodium intake at 3 months. Efficacy during the maintenance phase was diminished, possibly due to inadvertent adoption of the intervention by the control group. Funding Grant funding from the Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation. Trial registration Registered at ClinicalTrials.gov with study number NCT02132013.

This is a real-world evidence study that aims to analyze the efficacy, tolerability and safety profile of paritaprevir/ombitasvir/ritonavir and dasabuvir, in patients with renal impairment. We conducted an observational prospective study, on 232 patients with chronic kidney disease, undergoing treatment with paritaprevir/ombitasvir/ritonavir and dasabuvir, for chronic hepatitis C infection - genotype 1b. Renal and liver function were assessed at the beginning of therapy, monthly during treatment and three months after therapy completion. All patients achieved sustained virologic response. Common side effects were nausea, fatigue and headache. Close monitoring of tacrolimus blood levels and dose reduction was required in kidney transplant recipients. HCV therapy in the setting of renal dysfunction has always been a challenging topic. Direct-acting antivirals have shown promising effects, demonstrating good tolerance and efficacy in patients with HCV infection and renal impairment. Sustained virologic response within our study population was 100%.

BACKGROUND The incidence of nephrolithiasis in children and adolescents is increasing and appears to double every 10 years. The most important role of the pediatric nephrologist is to diagnose and modify various metabolic and non-metabolic risk factors, as well as prevent long-term complications especially in the case of recurrent nephrolithiasis. OBJECTIVE The purpose of this review is to summarize the existing literature on the etiology and management of pediatric nephrolithiasis. RESULTS The incidence of kidney stones is increasing; dietary and environmental factors are probably the main causes for this increased incidence. In most pediatric patients, the etiology for the kidney stones can be identified. Metabolic factors, such as hypercalciuria and hypocitraturia, urinary tract infection, and urinary stasis, constitute leading causes. Herein, we review the etiologies, diagnostic work-up, and treatment options for the most prevalent causes of kidney stones. The detrimental effects of excessive dietary sodium, reduced fluid intake, and the benefits of plant-based over animal-based protein consumption on urinary crystal formation are discussed. We also review the long-term complications. CONCLUSIONS Pediatric nephrologists have an important role in the diagnostic work-up and prevention of recurring nephrolithiasis.

Abstract Secondary hyperparathyroidism is part of the complex of chronic kidney disease-associated mineral and bone disorders (CKD-MBD) and is linked with high bone turnover, ectopic calcification, and increased cardiovascular mortality. Therefore, measures for CKD-MBD aim at lowering PTH levels, but there is no general consensus on optimal PTH target values. This manuscript is part of a pros and cons debate for keeping PTH levels within the normal range in children with CKD, focusing on the cons. We conclude that a modest increase in PTH most likely represents an appropriate adaptive response to declining kidney function in patients with CKD stages 2–5D, due to phosphaturic effects and increasing bone resistance. There is no evidence for strictly keeping PTH levels within the normal range in CKD patients with respect to bone health and cardiovascular outcome. In addition, the potentially adverse effects of PTH-lowering measures, such as active vitamin D and calcimimetics, must be taken into account. We suggest that PTH values of 1–2 times the upper normal limit (ULN) may be acceptable in children with CKD stage 2–3, and that PTH levels of 1.7–5 times UNL may be optimal in patients with CKD stage 4–5D. However, standard care of CKD-MBD in children relies on a combination of different measures in which the observation of PTH levels is only a small part of, and trends in PTH levels rather than absolute target values should determine treatment decisions in patients with CKD as recommended by the 2017 KDIGO guidelines.

In children with chronic kidney disease (CKD), optimal control of bone and mineral homeostasis is essential, not only for the prevention of debilitating skeletal complications and achieving adequate growth but also for preventing vascular calcification and cardiovascular disease. Complications of mineral bone disease (MBD) are common and contribute to the high morbidity and mortality seen in children with CKD. Although several studies describe the prevalence of abnormal calcium, phosphate, parathyroid hormone, and vitamin D levels as well as associated clinical and radiological complications and their medical management, little is known about the dietary requirements and management of calcium (Ca) and phosphate (P) in children with CKD. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists, who develop clinical practice recommendations (CPRs) for the nutritional management of various aspects of renal disease management in children. We present CPRs for the dietary intake of Ca and P in children with CKD stages 2-5 and on dialysis (CKD2-5D), describing the common Ca- and P-containing foods, the assessment of dietary Ca and P intake, requirements for Ca and P in healthy children and necessary modifications for children with CKD2-5D, and dietary management of hypo- and hypercalcemia and hyperphosphatemia. The statements have been graded, and statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. These CPRs will be regularly audited and updated by the PRNT.

After pediatric kidney transplantation BK polyomavirus (BKPyV) infections are associated with an increased risk of graft loss by BKPyV-associated nephropathy (BkPyVAN). However, suitable prognostic markers for the individual outcome of BKPyV infections are missing and the management of therapeutic interventions remains a challenge to the success of pediatric kidney transplantation. This review gives an overview on current diagnostic and therapeutic strategies in the field of BKPyV infections after pediatric kidney transplantation. Methods determining the individual immune response to BKPyV are described and their usability is discussed. There is growing evidence that BKPyV-specific T cells (BKPyV-Tvis) may serve as prognostic markers in order to steer immunosuppressive therapy in pediatric kidney recipients with BKPyV viremia in future. Prospective randomized trials in viremic kidney recipients comparing Tvis-steered therapeutic intervention with standard reduction of immunosuppression are needed before implementation of BKPyV-Tvis monitoring in routine care of BKPyV infections.

Abstract Background The objective of this study was to evaluate the prognostic role of postnatal acute kidney injury (AKI) on neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH). Methods This is a prospective observational study including all neonates with HIE receiving TH between 2009 and 2016 at a single center. AKI was classified according to the Kidney Disease: Improving Global Outcomes definition modified for neonatal age. Child development was assessed using the Griffiths Mental Development Scales (GMDS). Study outcome was defined as unfavorable outcome (including death or disability according to GMDS) or favorable otherwise, at 12 and 24 months. Results One-hundred and one neonates (median gestational age 39 weeks) were included. AKI was diagnosed in 10 neonates (10%). Seven patients died within the first year, 35 patients had disability at 12 months, and 45 patients at 24 months. AKI was associated with increased likelihood of unfavorable outcome at 24 months (100% vs. 59% in neonates without AKI; p = 0.01). AKI showed good positive predictive value (1.00, 95% CI 0.71–1.00) and specificity (1.00, 95% CI 0.88–1.00), but poor negative predictive value (0.41, 95% CI 0.30–0.52) and sensitivity (0.19, 95% CI 0.11–0.32) at 24 months. Conclusions AKI might be a reliable indicator of death or long-term disability in infants with HIE receiving TH, but the absence of AKI does not guarantee a favorable long-term outcome.

IgA nephropathy (IgAN) is one the most common primary glomerulonephritis in children and adolescents worldwide, with 20% of children developing end-stage kidney disease (ESKD) within 20 years of diagnosis. There is a need for treatment guidelines, especially for steroids in children with primary IgAN, since the STOP-IgA trial casts doubts on the use of steroids in adults with intermediate risk. Pediatricians are prone to prescribe steroids in addition to renin-angiotensin system blockade (RASB) when proteinuria is > 0.5 g/l, eGFR deteriorates < 70 ml/min/1.73 m2, or when a biopsy sample shows glomerular inflammation. Lack of randomized controlled trials (RCTs) in children with IgAN has led to an absence of consensus on the use of immunosuppressive agents in the treatment of progressive IgAN. This literature review evaluates the available evidence on steroid treatment in children with IgAN.

Abstract Background Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation. Methods A retrospective study of 58 children aged 1–17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log10 Geq/ml in > 50% of the samples during ≥ 6 months. Results At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5–6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7–13). Conclusions CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.

Abstract Background The prevalence of hyperuricemia is increasing in adults, while the prevalence among adolescents is seldom reported. Methods A cross-sectional survey by multistage, stratified sampling method was carried out in Shandong Province during 2017–2018. A total of 9371 adolescents aged from 13 to 19 years were randomly sampled and analyzed in this survey. Results The overall mean serum uric acid (sUA) concentration was 6.08 ± 1.57 mg/dL and overall hyperuricemia prevalence was 25.4% and 60.5% (when hyperuricemia was defined as sUA ≥ 7 mg/dL or ≥ 5.5 mg/dL). Prevalence were 42.3% (male) and 8.0% (female) when limit was 7 mg/dL and prevalence were 82.1% (male) and 38.4% (female) when limit was 5.5 mg/dL. Male gender, increased body mass index, increased waist circumstance, increased triglycerides, increased fasting blood glucose, increased systolic blood pressure, decreased estimated glomerular filtration rate, and positive family gout history were associated with the enhanced risk of hyperuricemia according to univariate and/or multivariate logistic regression analysis. Food intake frequency of carbonate beverage, mutton, and other kinds varied between hyperuricemia adolescents and normal sUA ones. Conclusions The studied adolescent population showed sUA level and hyperuricemia prevalence which are even higher than those of adults in China. The epidemic of youth hyperuricemia may pose a future threat of gout attacks and other hyperuricemia-related diseases, which alarms the public, health professionals and health policy makers to prepare the future health challenges.

Bacterial urinary tract infections (UTIs) are one of the most common reasons for children to be admitted to hospital. Bacteria infect and invade the bladder (the lower urinary tract) and if the infection disseminates to the upper urinary tract, significant inflammation in the kidneys may arise. Inflammation is a double-edged sword: it is needed to clear bacteria, but if excessive, kidney tissue is injured. During injury, nephrons are destroyed and replaced with deposition of extracellular matrix and a renal scar. In this review, we explore the pathogenesis of UTIs and discuss the risk factors that result in dissemination of bladder infection to the kidneys. Three major risk factors predispose to kidney infections: the presence of vesicoureteric reflux, the presence of bladder and bowel dysfunction, and defects in the ability of the host immune response to clear bacteria. In this review, we will discuss these factors, their relationship to renal scarring, and potential treatments that might be beneficial to prevent renal scar formation in children.

High prevalence of arterial hypertension is known in pediatric renal transplant patients, but how blood pressure (BP) distribution and control differ between age groups and whether sex and age interact and potentially impact BP after transplantation have not been investigated.

Abstract Dietary management in pediatric chronic kidney disease (CKD) is an area fraught with uncertainties and wide variations in practice. Even in tertiary pediatric nephrology centers, expert dietetic input is often lacking. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, was established to develop clinical practice recommendations (CPRs) to address these challenges and to serve as a resource for nutritional care. We present CPRs for energy and protein requirements for children with CKD stages 2–5 and those on dialysis (CKD2–5D). We address energy requirements in the context of poor growth, obesity, and different levels of physical activity, together with the additional protein needs to compensate for dialysate losses. We describe how to achieve the dietary prescription for energy and protein using breastmilk, formulas, food, and dietary supplements, which can be incorporated into everyday practice. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgment. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.

BACKGROUND Posterior urethral valves (PUVs) account for 17% of pediatric renal failure. The management of pregnancies involving fetuses with PUV is hampered by the fact that current clinical parameters obtained from fetal ultrasound and/or fetal urine biochemistry are insufficient to predict postnatal renal function. We previously have developed a fetal urine peptide signature (12PUV) that predicted with high precision postnatal renal failure at 2 years of age in fetuses with PUV. Here, we evaluated the accuracy of this signature to predict postnatal renal outcome in fetuses with PUV in an independent single-center study. METHODS Thirty-three women carrying fetuses with suspected PUV were included. Twenty-five fetuses received vesicoamniotic shunts during pregnancy. PUV was confirmed postnatally in 23 patients. Of those 23 fetuses, 2 were lost in follow-up. Four and 3 patients died in the pre- and perinatal periods, respectively. Follow-up renal function at 6 months of age was obtained for the remaining 14 patients. The primary outcome was early renal failure, defined by an eGFR < 60 mL/min/1.73 m2 before 6 months of age or pre- or perinatal death. RESULTS The peptide signature predicted postnatal renal outcome in postnatally confirmed PUV fetuses with an AUC of 0.94 (95%CI 0.74-1.0) and an accuracy of 90% (95%CI 78-100). The signature predicted postnatal renal outcome for the suspected PUV cases with an AUC of 0.89 (95%CI 0.72-0.97) and an accuracy of 84% (95%CI 71-97). CONCLUSIONS This single-center study confirms the predictive power of the previously identified 12PUV fetal urinary peptide signature.

BACKGROUND Rituximab (RTX) is efficient in steroid-dependent nephrotic syndrome (SDNS) in pediatric and adult patients. The aim of this study is to describe hypogammaglobulinemia as a side effect of RTX treatment. METHODS All pediatric patients (< 18 years old) of four French pediatric nephrology centers who received RTX for SDNS between 2010 and 2015 have been included. Clinical and biological data have been analyzed retrospectively before, during, and after RTX treatment. Hypogammaglobulinemia was defined as an IgG level < - 2 standard deviations for patient age. RESULTS A total of 107 pediatric patients have been included, 65.9% were boys, median age at nephrotic syndrome diagnosis was 3.1 interquartile range [IQ 2.24-5.45] years and age at RTX introduction was 11.7 [IQ 8.6-14.2] years. Twenty-one patients had hypogammaglobulinemia before the initiation of RTX. Of the patients, 25/86 had at least one hypogammaglobulinemia during B cell depletion or after B cell recovery while IgG levels at initiation were normal with a persisting hypogammaglobulinemia for 13 patients 1 year after B cell recovery. Patients who developed hypogammaglobulinemia were younger at RTX initiation with a median age of 8.2 years [IQ 6.3-12.4]. Among all the 46 patients with hypogammaglobulinemia during follow-up, 13 had a concomitant infection. CONCLUSIONS Hypogammaglobulinemia is a frequent complication of RTX treatment in younger children treated for SDNS. The use of RTX in children has to be carefully evaluated and their clinical and biological follow-up should be adapted to the age-dependent risk profile for hypogammaglobulinemia.

Growth retardation is a major feature of chronic kidney disease (CKD) of onset in infants or children and is associated with increased morbidity and mortality. Several factors have been shown to play a causal role in the growth impairment of CKD. All these factors interfere with growth by disturbing the normal physiology of the growth plate of long bones. To facilitate the understanding of the pathogenesis of growth impairment in CKD, this review discusses cellular and molecular alterations of the growth plate during uremia, including structural and dynamic changes of chondrocytes, alterations in their process of maturation and hypertrophy, and disturbances in the growth hormone signaling pathway.

More and more studies demonstrated that genetic variation at C1GALT1 influences Gd-IgA1 level in IgAN. However, whether the expression of β1, 3-galactosyltransferase (β1, 3Gal-T) was influenced may provide insights into how Gd-IgA1 levels are controlled in IgAN. Thirty IgAN patients diagnosed in Tianjin Medical University General Hospital from April to September 2018 and 30 healthy volunteers whose age and gender matched with patients were enrolled in this study. Total Gd-IgA1 levels in plasma were determined by ELISA and C1GALT1 levels were determined by RT-PCR. Four databases (PubMed, EMBASE, CNKI, WanFang Medical Network) were searched to identify eligible studies that evaluated a difference in the expression of C1GALT1 in IgAN patients compared with total controls (non-IgAN and health controls). The C1GALT1C1 expression levels, which was indispensable to β1, 3Gal-T of IgA1, was also been compared. Gd-IgA1 levels were remarkable higher in IgAN patients compared with healthy control. The expression levels of C1GALT1 gene were remarkably down-regulated in IgAN patients compared with healthy control. And the mRNA level of C1GALT1 was inversely correlated to Gd-IgA1 levels. In meta-analysis, six articles including 316 participants that analyzed the expression of β1, 3Gal-T were met inclusion criteria. There was no significant difference in the expression of C1GALT1 between IgAN patients compared with controls. And we found patients with IgAN had lower levels of C1GALT1 gene expression in the B cells compared to controls. The C1GALT1C1 levels in the IgAN patients were not different from the levels in the control group, which were unchanged no matter according to different ethnic population, different control group and different cell source. Two studies including 46 persons compared enzymatic activity of β1, 3Gal-T in B cells, and the result showed the β1, 3Gal-T activity was decreased in B cells. We found expression levels of C1GALT1 were remarkably downregulated in IgAN patients and negatively correlated with higher levels of Gd-IgA1. Subsequent meta-analysis validated the low expression and activity of β1, 3Gal-T in B cells in patients with IgAN. However, there was no apparent disparity in the aspect of C1GALT1C1 expression between IgAN and control groups.

Acute kidney injury (AKI) is commonly defined using the KDIGO system, which includes criteria based on reduced urine output (UO). There is no consensus on whether UO should be measured using consecutive hourly readings or mean output. This makes KDIGO UO definition and staging of AKI vulnerable to inconsistency which has implications both for research and clinical practice. The objective of this study was to investigate whether the way in which UO is defined affects incidence and staging of AKI. We conducted a retrospective analysis of two single centre observational studies investigating (i) patients undergoing cardiac surgery and (ii) patients admitted to general intensive care units (ICU). AKI was identified using KDIGO serum creatinine (SCr) criteria and two methods of UO (UOcons: UO meeting KDIGO criteria in each consecutive hour; UOmean: mean hourly UO meeting KDIGO criteria). Data from 151 CICU and 150 ICU admissions were analysed. Incidence of AKI using SCr alone was 23.8% in CICU and 32% in ICU. Incidence increased in both groups when UO was considered, with inclusion of UOmean more than doubling reported incidence of AKI (CICU: UOcons 39.7%, UOmean 72.8%; ICU: UOcons 51.3%, UOmean 69.3%). In both groups UOcons led to a larger increase in KDIGO stage 1 but UOmean increased the incidence of KDIGO stage 2. We demonstrate a serious lack of clarity in the internationally accepted AKI definition leading to significant variability in reporting of AKI incidence.

Chronic kidney disease (CKD) is a substantial cause of morbidity and mortality worldwide with disproportionate effects in sub-Saharan Africa (SSA). The optimal methods to estimate glomerular filtration rate (GFR) and therefore to determine the presence of CKD in SSA are uncertain. We plan to measure iohexol excretion to accurately determine GFR in Malawi, South Africa and Uganda. We will then assess the performance of existing equations to estimate GFR and determine whether a modified equation can better improve estimation of GFR in sub-Saharan Africa. The African Research on Kidney Disease (ARK) study is a three-country study embedded within existing cohorts. We seek to enrol 3000 adults > 18 years based on baseline serum creatinine. Study procedures include questionnaires on socio-demographics and established risk factors for kidney disease along with anthropometry, body composition, blood pressure, blood chemistry and urine microscopy and albuminuria. We will measure GFR (mGFR) by plasma clearance of iohexol at 120, 180 and 240 min. We will compare eGFR determined by established equations with mGFR using Bland-Altman plots. We will use regression methods to estimate GFR and compare the newly derived model with existing equations. Through the ARK study, we aim to establish the optimal approach to estimate GFR in SSA. The study has the advantage of drawing participants from three countries, which will increase the applicability of the findings across the region. It is also embedded within established cohorts that have longitudinal information and serial measures that can be used to characterize kidney disease over a period of time. This will help to overcome the limitations of previous research, including small numbers, selected population sub-groups, and lack of data on proteinuria. The ARK collaboration provides an opportunity for close working partnerships across different centres, using standardized protocols and measurements, and shared bio-repositories. We plan to build on the collaboration for this study for future work on kidney disease in sub-Saharan Africa, and welcome additional partners from across the continent.

Acute tubulointerstitial nephritis (AIN) is an uncommon cause of acute kidney injury in children, accounting for less than 10% of cases. There is limited information regarding the range of underlying diagnoses and how these may differ geographically. We undertook a retrospective case note review of consecutive cases of biopsy-proven AIN, presenting to a single UK tertiary paediatric centre, to describe the range of AIN in our caseload, define key characteristics and response to treatment, with the aim of informing paediatric nephrology practice. Cases were identified retrospectively from departmental records. Data extracted included demographics, presenting clinical and biochemical features, renal biopsy histology, treatment and follow-up. Ten cases were identified over 8 years (2007–2014). Age range 6–16 years. Male:Female ratio 1:9. Final diagnoses included 6 tubulointerstitial nephritis and uveitis syndrome (TINU), 2 idiopathic, 1 sarcoidosis, 1 child with Streptococcal disease. Of the TINU cases, timing of eye symptoms varied in relation to AIN presentation. Cases had a varied investigative work-up. Median presenting plasma creatinine was 303 μmol/l (range 152–932 μmol/l). Renal function improved spontaneously in 1 idiopathic case and improved with antimicrobial treatment in a child with Streptococcal disease. Eight cases received immunosuppressive treatment with intravenous methylprednisolone (approximately 10 mg/kg for 3–5 days) and / or oral prednisolone (1–2 mg/kg initially, reducing over 7–28 days). At 1 month, median creatinine had fallen to 91 μmol/l (range 41–120 μmol/l) with median eGFR 61 ml/min/1.73m2 (range 51-103 ml/min/1.73m2). At last follow-up (median 18.5 months, range 2–70 months), median creatinine was 71 μmol/l (range 47–90 μmol/l) with median eGFR 80 ml/min/1.73m2, range 63 to 101 ml/min/1.73m2). Two patients received antihypertensives at diagnosis and 1 further patient at 1 month follow-up. Eight patients received electrolyte supplementation. Median time to discontinuing electrolyte supplementation was 3.5 months (range 1–12 months). To our knowledge, this is the only contemporary UK case series of biopsy-proven AIN in children. Our population has a high proportion of TINU. Treatment was accompanied by improvement of renal function, however 7/10 patients had an eGFR < 90 ml/min/1.73m2 at last follow-up. We suggest a standardised investigative work-up and recommend long-term follow-up.

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. Chronic exposure to intermittent hemodialysis may be a source of added stress to the cardiovascular system; intradialytic hypotension is a common complication of hemodialysis, and repeated events may lead to hemodynamic stress and ischemic injuries. Administration of non-pneumatic compression stockings to the lower limbs has demonstrated hemodynamic stabilizing effects in other settings and may provide similar benefits in the kidney disease population. Therefore, we conducted this pilot study assessing the feasibility and tolerability of the application of non-pneumatic compression stockings to patients with kidney disease. We also assessed the changes in hemodynamic measurements following the application of the compression stockings to explore the biological feasibility of this being an effective intervention for intradialytic hypotension. Fifteen individuals were enrolled in the study (5 healthy, 5 chronic kidney disease patients, and 5 dialysis patients). Outcomes including hemodynamic parameters such as cardiac output, peripheral vascular resistance, and blood pressure were measured using continuous pulse wave analysis. Changes in global longitudinal strain were measured via echocardiography. These outcome measurements were made before and after the application of compression stockings. All study participants tolerated the compression garments well and without complication. Hemodynamic response to lower body compression caused varying effects on cardiac output, mean arterial pressure and global longitudinal strain. Some individuals saw large improvements in hemodynamic parameters while in others the opposite effect was observed. No consistent response was elicited. Application of compression stockings to patients with renal dysfunction is well-tolerated. However, significant variations in hemodynamic outcomes exist, and may be a barrier for larger scale trials without prior identification of specific patient characteristics indicating likely benefit from the application of external compression. ClinicalTrials.gov, Identifier: NCT02915627, Registration Date: Sept 27, 2016.

End stage kidney disease and hemodialysis dependence are associated with impairments in health-related quality of life (HRQOL), which may be related to vascular access (VA). Few HRQOL measures are VA-specific and none differentiate HRQOL impact by VA type. We developed a VA-targeted HRQOL measure to distinguish the impact of fistulas, grafts and catheters. We created an initial item pool based on literature review and then conducted focus groups at 4 US sites with 37 adults and interviews with nine dialysis clinicians about VA’s impact on HRQOL. We then drafted the Hemodialysis Access-Related Quality of Life (HARQ) measure and cognitively tested it with 17 hemodialysis patients. Focus group and cognitive interview participants were diverse in age, gender, years on dialysis, and VA. We identified six domains for the HARQ: symptoms, physical functioning, emotional impacts, social and role functioning, sleep, and care-related burdens. Cognitive interviews indicated that items were easily understood and supported content validity. Attributing HRQOL impact to VA as opposed to other hemodialysis burden was challenging for some items. Some items were dropped that were considered redundant by patients, limitations while dressing was added, and reference to VA-specific impact was included for each item. The average Flesch-Kincaid reading grade level for the revised 47-item HARQ was 5.3. The HARQ features VA-specific content not addressed in other HRQOL measures, making it ideal for comparisons of different VA types and new VA technologies. The psychometric properties of the HARQ will be evaluated in future research.

With the emergence of electronic health records, the reuse of clinical data offers new perspectives for the diagnosis and management of patients with rare diseases. However, there are many locks for the repurposing of clinical data. The development of decision support systems depends on the ability: to recruit patients; then to extract and integrate the patients’ data; to mine and stratify these data; and to integrate the decision support algorithm into the patient care. This last step requires an adaptability of the electronic health records to integrate learning health system tools. In this literature review we examine the research that provide solutions to unlock these barriers and accelerate translational research: structured electronic health records and free text search engine to find patients, data warehouses and natural language processing to extract the phenotypes, machine learning algorithms to classify patients, similarity metrics to diagnose patients etc. Medical informatics is experiencing an impellent request to develop decision support systems and this requires ethical considerations for clinicians and patients to ensure a good usage of health data.

Eosinophils in kidney disease are poorly understood and are often incidental findings on kidney biopsy. Eosinophilia in blood and renal biopsy tissue is associated with a host of immune and non-immune kidney diseases. The significance of eosinophilia in renal diseases has not been well addressed. We evaluated the presence of peripheral eosinophilia (> 4% of blood leukocytes) with biopsy tissue eosinophilia and their association with end-stage-kidney-disease (ESKD). A nested case-control (2:1) of patients who underwent kidney biopsies at Johns Hopkins Hospital and Medical University of South Carolina from 2004 to 2018 were included in the study. From the 616 eligible patients, 178 patients were identified through the registry of kidney biopsies as 18 years or older without missing biopsy reports or hematology results. Controls (n = 154) had no ESKD at the time of case (n = 24) designation and were assembled using incident density sampling and matched on age and sex. The association of peripheral eosinophilia (> 4% of peripheral blood leukocytes) with the risk of progression to ESKD was evaluated using conditional logistic model after adjusting for clinical demographics. Among 178 patients, 65 (37%) had peripheral eosinophilia and 113 (63%) had no eosinophilia. Compared to patients without eosinophilia, patients with peripheral eosinophilia were notably male and had a higher serum creatinine at the time of their biopsy. Peripheral eosinophilia was associated with higher risk of ESKD (OR 15.9 [1.9, 134.7]) adjusted for patient demographics including hypertension, proteinuria and eGFR at the time of kidney biopsy. Peripheral eosinophilia had a significant linear association with kidney tissue eosinophils, 22 (standard deviation [SD] 20) per high power field (hpf) in 4–10% peripheral eosinophilia, 19 (SD 18) per hpf in ≥10% eosinophilia and 3 (SD 7) per hpf in no eosinophilia (P < 0.001). Peripheral eosinophilia is an independent predictor of tissue eosinophilia and subsequent progression to ESKD. Peripheral eosinophilia may be an early biomarker for underlying inflammation and disease, but further studies to investigate this clinical association are warranted.

Transfer from a pediatric to an adult medical setting is associated with many barriers. Additionally, there are little data on patients’ assessment of the transition process itself. 3 years ago at Lurie Children’s Hospital of Chicago, we established a kidney transition program with the help of an adult nephrologist, physician assistant (PA) and social worker (LCSW). After 18 months, we evaluated the patients’ perception of the program as part of a continuous quality initiative process. Patients who had transitioned from pediatric care and were seen at least once in the adult nephrology clinic were anonymized and asked to take an established 5-point Likert scale survey. Survey questions addressed readiness to transition, the transition process itself, and the perception of adult care. Surveys were followed with semi-structured interviews. 3 readers rated each response as either “negative,” “neutral,” or “positive.” Average, standard deviation and reader reliability were calculated. The readers also selected a word that best depicted each response and those most-common words were counted by question and overall. 17 out of 42 patients (40%) completed the survey. Average age at transition (mean + SD) was 20 + 2 years; the majority of patients (82%) felt ready to transfer to adult care but only 59% felt they were consulted on the timing. 88% of patients felt having a transition appointment and meeting the adult care providers in the pediatric setting to be valuable. Although 94% of patients ultimately felt comfortable in the adult care environment, 18% experienced noticeable differences in treatment recommendations. 13 semi-structured interviews were conducted. Overall, the patients responded positively (3 + 0, 100% reader reliability) to the transition. But, when asked what could have improved the transition, the word the patients used most was, “earlier.” Young adults (YA) transitioning to adult care often feel ready to transition earlier than their transfer of care date. They subjectively benefit from a transition program that outlines the process of transferring their care. Many YA patients would benefit from a transition program that bolsters patient independence during early adult care visits.

Chronic kidney disease (CKD) disease affects gut flora by causing dysbiosis and lead to systemic inflammatory conditions. Here, we provide intestinal flora changes of CKD patients undertook different hemodialysis therapy. From 2017 to 2019, a total of 166 patients from Guangzhou Red Cross Hospital were recruited and divided into four groups with 17 cases in healthy control group, 47 cases in CKD non-dialysis group, 49 cases in HD group, and 53 cases in PD group. Intestinal flora genome 16S rDNA sequencing and further bio-informatic analysis were performed. Decreased diversity and altered communities of intestinal flora in PD patients, in which microbial diversity was positive correlated with the albumin level were observed. A total of 20 intestinal flora phyla were detected in 166 fecal samples, divided into 3 dominant intestinal types including Bacteroides-dominant gut type, Firmicutes-dominant type and Proteobacteria-dominant gut type. Further analyses found 198 genera, the abundance of 86 genera were significantly different. Butyrate-producing taxa as Faecalibacterium in genera level and Bifidobacteriaceae and Prevotellaceae in family level were dominant genus in CT, CKD, and HD groups, while urease containing-, indole- and p-cresol-forming taxa as Escherichia in genera and Enterobacteriaceae, Enterococcaceae in family level was dominated genus in PD group. Number of differential expressed genes in KEGG enrichment pathways were significantly different in PD group in carbohydrate metabolism, amino acid metabolism, energy metabolism, translation, and membrane transport. Our results suggest peritoneal dialysis therapy could result in reduced diversity and altered microbial communities, with reduced probiotic butyrate-producing taxa and increased urease containing-, indole- and p-cresol-forming taxa. The disordered intestinal flora can seriously affect the nutrition level in CKD patients with PD therapy.

The long-term predictive ability of acute kidney injury (AKI) classification based on “Kidney Disease: Improving Global Outcomes”(KDIGO) AKI diagnosis criteria has not been clinically validated in diffuse proliferative lupus nephritis (DPLN) patients with AKI. Our objective was to assess the long-term predictive value of KDIGO AKI classification in DPLN patients with AKI. Retrospective cohort study was conducted by reviewing medical records of biopsy-proven DPLN patients with AKI from the First Affiliated Hospital of Wenzhou Medical University between Jan 1, 2000 and Dec 31, 2014. Multivariate Cox regression and survival analysis were performed. One hundred sixty-seven DPLN patients were enrolled,82(49%) patients were normal renal function (No AKI), 40(24%) patients entered AKI-1 stage (AKI-1), 26(16%) patients entered AKI-2 stage (AKI-2) and 19(16%) patients entered AKI-3 stage (AKI-3). The mean follow-up of all patients was 5.1 ± 3.8 years. The patient survival without ESRD of all patients was 86% at 5 years and 79% at 10 years. The patient survival rate without ESRD at 10 yr was 94.5% for No AKI patients, 81.8% for AKI-1 patients, 44.9% for AKI-2 patients and 14.6% for AKI-3 patients. The area under the ROC curve for KDIGO AKI classification to predict the primary end point was 0.83 (95% CI: 0.73–0.93) (P < 0.001). In Cox regression analysis, AKI stage was independently associated with primary endpoint, with an adjusted hazard ratio (HR) of 3.8(95% CI 2.1–6.7, P < 0.001). Severity of AKI based on KDIGO AKI category was associated with progression to ESRD in DPLN patients. Analytical data also confirmed the good discriminative power of the KDIGO AKI classification system for predicting long-term prognosis of DPLN patients with AKI.

Rationale & Objective Peritoneal dialysis (PD)-related peritonitis carries high morbidity for PD patients. Understanding the characteristics and risk factors for peritonitis can guide regional development of prevention strategies. We describe peritonitis rates and the associations of selected facility practices with peritonitis risk among countries participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS). Study Design Observational prospective cohort study. Setting & Participants 7,051 adult PD patients in 209 facilities across 7 countries (Australia, New Zealand, Canada, Japan, Thailand, United Kingdom, United States). Exposures Facility characteristics (census count, facility age, nurse to patient ratio) and selected facility practices (use of automated PD, use of icodextrin or biocompatible PD solutions, antibiotic prophylaxis strategies, duration of PD training). Outcomes Peritonitis rate (by country, overall and variation across facilities), microbiology patterns. Analytical Approach Poisson rate estimation, proportional rate models adjusted for selected patient case-mix variables. Results 2,272 peritonitis episodes were identified in 7,051 patients (crude rate, 0.28 episodes/patient-year). Facility peritonitis rates were variable within each country and exceeded 0.50/patient-year in 10% of facilities. Overall peritonitis rates, in episodes per patient-year, were 0.40 (95% CI, 0.36-0.46) in Thailand, 0.38 (95% CI, 0.32-0.46) in the United Kingdom, 0.35 (95% CI, 0.30-0.40) in Australia/New Zealand, 0.29 (95% CI, 0.26-0.32) in Canada, 0.27 (95% CI, 0.25-0.30) in Japan, and 0.26 (95% CI, 0.24-0.27) in the United States. The microbiology of peritonitis was similar across countries, except in Thailand, where Gram-negative infections and culture-negative peritonitis were more common. Facility size was positively associated with risk for peritonitis in Japan (rate ratio [RR] per 10 patients, 1.07; 95% CI, 1.04-1.09). Lower peritonitis risk was observed in facilities that had higher automated PD use (RR per 10 percentage points greater, 0.95; 95% CI, 0.91-1.00), facilities that used antibiotics at catheter insertion (RR, 0.83; 95% CI, 0.69-0.99), and facilities with PD training duration of 6 or more (vs <6) days (RR, 0.81; 95% CI, 0.68-0.96). Lower peritonitis risk was seen in facilities that used topical exit-site mupirocin or aminoglycoside ointment, but this association did not achieve conventional levels of statistical significance (RR, 0.79; 95% CI, 0.62-1.01). Limitations Sampling variation, selection bias (rate estimates), and residual confounding (associations). Conclusions Important international differences exist in the risk for peritonitis that may result from varied and potentially modifiable treatment practices. These findings may inform future guidelines in potentially setting lower maximally acceptable peritonitis rates.

Early identification of people with CKD in primary care, particularly those with risk factors such as diabetes and hypertension, enables proactive management and referral to specialist services for progressive disease. The 2019 NHS Long Term Plan endorses the development of digitally-enabled services to replace the ‘unsustainable’ growth of the traditional out-patient model of care.Shared views of the complete health data available in the primary care electronic health record (EHR) can bridge the divide between primary and secondary care, and offers a practical solution to widen timely access to specialist advice. We describe an innovative community kidney service based in the renal department at Barts Health NHS Trust and four local clinical commissioning groups (CCGs) in east London. An impact evaluation of the changes in service delivery used quantitative data from the virtual CKD clinic and from the primary care electronic health records (EHR) of 166 participating practices. Survey and interview data from health professionals were used to explore changes to working practices. Prior to the start of the service the general nephrology referral rate was 0.8/1000 GP registered population, this rose to 2.5/1000 registered patients by the second year of the service. The majority (> 80%) did not require a traditional outpatient appointment, but could be managed with written advice for the referring clinician. The wait for specialist advice fell from 64 to 6 days. General practitioners (GPs) had positive views of the service, valuing the rapid response to clinical questions and improved access for patients unable to travel to clinic. They also reported improved confidence in managing CKD, and high levels of patient satisfaction. Nephrologists valued seeing the entire primary care record but reported concerns about the volume of referrals and changes to working practices. ‘Virtual’ specialist services using shared access to the complete primary care EHR are feasible and can expand capacity to deliver timely advice. To use both specialist and generalist expertise efficiently these services require support from community interventions which engage primary care clinicians in a data driven programme of service improvement.

Due to these changes in kidney function, aging kidneys are more prone to drug-induced impairments in renal properties. Diabetes has been associated with the declined kidney function and an elevated risk of renal failure. The aim of this study is to compare kidney function and potentially nephrotoxic drug use among home-dwelling older persons with or without diabetes. A total of 259 persons with and 259 persons without diabetes and aged ≥65 years were randomly selected to participate in a health examination with complete data gathered from 363 individuals (187 with diabetes and 176 without diabetes). The estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Each participant was categorized based on the nephrotoxic profile of their medications. There were no differences in mean eGFR values (77.5 ± 18.8 vs. 80.5 ± 14.8 ml/min/1.73m2, p = 0.089) or in the proportion of participants with eGFR < 60 ml/min/1.73m2 among persons with diabetes (16% vs. 10%, p = 0.070), compared to persons without diabetes. Potentially nephrotoxic drug use was similar between the groups. The mean number of potentially nephrotoxic drugs was 1.06 ± 0.88 in those with and 0.97 ± 1.05 in those without diabetes (p = 0.39). The kidney function of older persons with diabetes does not differ from that of older persons without diabetes and furthermore potentially nephrotoxic drug use seem to play only a minor role in the decline in kidney function among home-dwelling persons in the Inner-Savo district.

The impact of length of hospital stay on activities of daily living (ADLs) has not specifically been investigated among dialysis patients. Therefore, we attempt to verify the association between the length of hospital stay and the decline in ADLs among hemodialysis patients. This prospective cohort study used data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS). We included 2442 hemodialysis patients aged ≥40 years from the J-DOPPS phase V (2012–2015) and subsequently excluded those who had already lost basic activities of daily living (BADLs) as demonstrated by dependency in at least three of the five BADLs at baseline and for whom changes in ADLs had been evaluated for less than 90 days. The main exposure was the cumulative length of hospital stay during the follow-up period. The primary outcomes were a decline in at least one of the five BADLs and eight instrumental activities of daily living (IADLs). We compared risk ratios (RRs) for 30-day increments for hospital stays with 10-year increments for age and having diabetes. A total of 849 patients were included in the statistical analysis. The cumulative length of hospital stay was significantly associated with a risk of decline in ADLs (adjusted RRs [95% confidence intervals] per 30-day increments: 1.42 [1.15 to 1.75] for BADLs, 1.38 [1.13 to 1.68] for IADLs). The adjusted RRs [95% CI] for 10-year increments in age were 1.20 [0.96 to 1.50] and 1.21 [1.00 to 1.47]. The adjusted RRs [95% CI] for having diabetes were 1.36 [0.97 to 1.91] for BADLs and 1.38 [1.04 to 1.84] for IADLs. The impact of a 30-day increment in the cumulative length of hospital stay on the decline in ADLs was comparable to that of a 10-year increase in age and having diabetes.

Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies. Computerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment. From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.

Impaired physical function due to muscle weakness and exercise intolerance reduces the ability to perform activities of daily living in patients with end-stage kidney disease, and by consequence, Health-Related Quality of Life (HRQoL). Furthermore, the risk of falls is an aggregate of physical function and, therefore, could be associated with HRQoL as well. The present study examined the associations between objective and subjective measures of physical function, risk of falls and HRQoL in haemodialysis patients. This cross-sectional multicentre study included patients on maintenance haemodialysis. Physical function (quadriceps force, handgrip force, Sit-to-Stand, and six-minute walking test), the risk of falls (Tinetti, FICSIT-4, and dialysis fall index) and HRQoL (PROMIS-29 and EQ-5D-3 L) were measured and analysed descriptively, by general linear models and logistic regression. Of the 113 haemodialysis patients (mean age 67.5 ± 16.1, 57.5% male) enrolled, a majority had impaired quadriceps force (86.7%) and six-minute walking test (92%), and an increased risk of falls (73.5%). Whereas muscle strength and exercise capacity were associated with global HRQoL (R2 = 0.32) and the risk of falls, the risk of falls itself was related to psycho-social domains (R2 = 0.11) such as depression and social participation, rather than to the physical domains of HRQoL. Objective measures of physical function were not associated with subjective fatigue, nor with subjective appreciation of health status. More than muscle strength, lack of coordination and balance as witnessed by the risk of falls contribute to social isolation and HRQoL of haemodialysis patients. Mental fatigue was less common than expected, whereas, subjective and objective physical function were decreased.

Dialysis patients who miss treatments are twice as likely to visit emergency departments (EDs) compared to adherent patients; however, prospective studies assessing ED use after missed treatments are limited. This interdisciplinary pilot study aimed to identify social determinants of health (SDOH) associated with missing hemodialysis (HD) and presenting to the ED, and describe resource utilization associated with such visits. We conducted a prospective observational study with a convenience sample of patients presenting to the ED after missing HD (cases); patients at local dialysis centers identified as HD-compliant by their nephrologists served as matched controls. Patients were interviewed with validated instruments capturing associated risk factors, including SDOH. ED resource utilization by cases was determined by chart review. Chi-square tests and ANOVA were used to detect statistically significant group differences. All cases visiting the ED had laboratory and radiographic studies; 40% needed physician-performed procedures. Mean ED length of stay (LOS) for cases was 17 h; 76% of patients were admitted with average LOS of 6 days. Comparing 25 cases and 24 controls, we found no difference in economic stability, educational attainment, health literacy, family support, or satisfaction with nephrology care. However, cases were more dependent on public transport for dialysis (p = 0.03). Despite comparable comorbidity burdens, cases were more likely to have impaired mobility, physical limitations, and higher severity of pain and depression. (p < 0.05). ED visits after missed HD resulted in elevated LOS and admission rates. Frequently-cited SDOH such as health literacy did not confer significant risk for missing HD. However, pain, physical limitations, and depression were higher among cases. Community-specific collaborations between EDs and dialysis centers would be valuable in identifying risk factors specific to missed HD and ED use, to develop strategies to improve treatment adherence and reduce unnecessary ED utilization.

Several factors such as recipient age, BMI, serum cratinine, and positive history of dialysis are important in predicting graft survival among kidney transplant recipients. One factor affecting the transplant outcomes is donors and recipients gender, which is usually ignored. A total of 1113 kidney transplant recipients were studied in this retrospective cohort study. Several factors were taken into account for graft survival and outcomes such as donors and recipients gender and age in addition to common recipient factors like cratinine, eGFR, BMI, and positive history of dialysis. The most successful transplant based on donor-recipient gender was observed in male donor to male recipient, and then male donor to female recipient. In female transplant recipients, level of serum cratinine and eGFR, positive dialysis history before transplant, and low donor hemoglobin level can be considered as good prognostic factors recommended for kidney transplant survival. Our results suggested gender matching for kidney transplant. Only in some exceptional conditions, male donor to female recipient kidney transplant may be successful and female donors to male recipients are not suggested, especially in aged patients with the history of dialysis.

Dual kidney transplantation (DKT) offers a way to extend the use of kidneys from expanded criteria donors (ECDs). Here, we compared the outcomes of DKT with those of single kidney transplantation from standard criteria donors (SCDs) and ECDs. In 2014, we began performing DKT using both kidneys from deceased donors greater than 70 years of age with one of two risk factors: serum creatinine (sCr) level over 3.0 mg/dl or eGFR under 30 ml/min. By 2017, we had performed 15 DKTs. We compared the outcomes of the 15 DKT recipients with those of 124 patients who received a kidney from an SCD and 80 patients who received a kidney from an ECD. Compared with ECDs and SCDs, DKT donors were older, had a higher diabetes burden, and a higher sCr level (p < 0.01, < 0.01, and 0.03, respectively). DKT recipients were also older and had a higher diabetes burden than recipients of kidneys from ECDs and SCDs (p < 0.01, both). DKT recipients had a lower nadir sCr and shorter duration to nadir sCr than single ECD KT recipients (p < 0.01and 0.04, respectively). The survival rates of DKT grafts were compatible with those of single KT grafts. Therefore, DKT may be considered a suitable an option to expand the donor pool.

Due to an unfortunate error during the processing of the article, the spelling of the second author name was incorrect.

Arthrogryposis, renal dysfunction, and cholestasis syndrome is a rare autosomal recessive disorder caused by mutations in the VPS33B and VIPAR genes. Most cases are fatal within the first year of life. Here we describe one of the two oldest patients with arthrogryposis, renal dysfunction, and cholestasis syndrome. This is a 12-year-old Hispanic female, from a non-consanguineous parents, diagnosed with an incomplete phenotype of arthrogryposis, renal dysfunction, and cholestasis syndrome with arthrogryposis and renal tubular dysfunction but without cholestasis. At 11 years of age, she was found to have impaired renal function, nephrotic-range proteinuria, Fanconi syndrome, and distal renal tubular acidosis. She also had hypercalciuria, nephrogenic diabetes insipidus, and small kidneys by renal ultrasound. Genetic analysis using whole exome sequencing showed a mutation and a partial deletion in the VPS33B gene. Further studies showed that the mother has a partial deletion in the VPS33B gene. Her medication regimen includes potassium citrate and enalapril.

Acid-base homeostasis is one of the most tightly regulated systems in the body. Maintaining the acid-base balance is particularly challenging for preterm infants and growing neonates. The kidney, which represents the crucial ultimate line of defense against disturbances of acid-base balance, undergoes a complex maturation process during the transition from a fetal to an extra-uterine environment. This review article summarizes the physiology of acid-base regulation by the immature human kidney and discusses disorders of acid-base balance, such as metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. In conditions of metabolic acidosis, the serum anion gap and the urinary anion gap can be useful tools to define the nature of the acidosis. Metabolic acidosis can reflect a decrease in glomerular filtration rate, or be the consequence of selective disorders of proximal or distal tubular function. Most tubulopathies associated with metabolic acidosis observed in neonates are primary, hereditary, isolated tubulopathies. Proximal renal tubular acidosis is characterized by bicarbonate wasting, while the distal types of renal tubular acidosis are secondary to distal acidification defects. All tubulopathies are associated with hypokalemia, with the exception of type 4 hyperkalemic distal renal tubular acidosis. The transporter defects in the various acid-base tubulopathies are now well defined. Treatment of the acidosis varies according to the site and mechanism of the defect. Chronic renal tubular acidosis or alkalosis severely impair growth and calcium metabolism. Early rational therapeutic intervention can prevent some of the consequences of the disorders and improves the prognosis.

BACKGROUND The management of IgA vasculitis with nephritis (IgAVN) remains controversial because of the difficulty to identify prognostic factors. This study reports the prognosis of children with IgAVN in relation to histological parameters. METHODS All children with IgAVN diagnosed between 2000 and 2015 in three pediatric nephrology centers were included. The following histological parameters were analyzed: mesangial proliferation (MP), endocapillary proliferation (EP), crescents, active, or chronic tubular and interstitial lesions (TIa lesions/TIc lesions), and segmental glomerulosclerosis (GS). Clinical and biological data were collected at the time of renal biopsy. The primary endpoint was IgAVN remission defined as a proteinuria < 200 mg/l without renal failure. RESULTS One hundred fifty-nine children were included with a median age of 7.6 years. Acute glomerular or TI lesions including MP, EP, crescents, and TIa lesions were observed, respectively, in 81%, 86%, 49%, and 21% of patients. Chronic glomerular lesions including GS and TIc lesions were observed in 6 and 7% of patients. Median initial proteinuria was 330 mg/mmol, albuminemia 32 g/l, and eGFR 110 ml/min/1.73 m2. One hundred twelve (70%) patients were in remission at the end of a median follow-up of 37.4 months. Chronic lesions were significantly associated with the absence of remission in multivariate analysis, whereas EP, crescents and TIa were not associated with a poor prognosis. CONCLUSIONS Of children with IgAVN, 30% present a persistent renal disease at the end of a 3-year follow-up. Chronic histological lesions, but not EP or crescents, are associated with a bad prognosis and must be evaluated in IgAVN histological classification.

BACKGROUND The specificity of the leukocyte esterase test (87%) is suboptimal. The objective of this study was to identify more specific screening tests that could reduce the number of children who unnecessarily receive antimicrobials to treat a presumed urinary tract infection (UTI). METHODS Prospective cross-sectional study to compare inflammatory proteins in blood and urine samples collected at the time of a presumptive diagnosis of UTI. We also evaluated serum RNA expression in a subset. RESULTS We enrolled 200 children; of these, 89 were later demonstrated not to have a UTI based on the results of the urine culture obtained. Urinary proteins that best discriminated between children with UTI and no UTI were involved in T cell response proliferation (IL-9, IL-2), chemoattractants (CXCL12, CXCL1, CXCL8), the cytokine/interferon pathway (IL-13, IL-2, INFγ), or involved in innate immunity (NGAL). The predictive power (as measured by the area under the curve) of a combination of four urinary markers (IL-2, IL-9, IL-8, and NGAL) was 0.94. Genes in the pathways related to inflammation were also upregulated in serum of children with UTI. CONCLUSIONS Urinary proteins involved in the inflammatory response may be useful in identifying children with false positive results with current screening tests for UTI; this may reduce unnecessary treatment.

Proper renal function relies on the tightly regulated development of nephrons and collecting ducts. This process, known as tubulogenesis, involves dynamic cellular and molecular changes that instruct cells to form highly organized tubes of epithelial cells which compartmentalize the renal interstitium and tubular lumen via assembly of a selective barrier. The integrity and diversity of the various renal epithelia is achieved via formation of intercellular protein complexes along the apical-basal axis of the epithelial cells. In recent years, the evolutionarily conserved family of Grainyhead-like (GRHL) transcription factors which encompasses three mammalian family members (Grainyhead-like 1, 2, 3) has emerged as a group of critical regulators for organ development, epithelial differentiation, and barrier formation. Evidence from transgenic animal models supports the presence of Grainyhead-like-dependent transcriptional mechanisms that promote formation and maintenance of epithelial barriers in the kidney. In this review, we highlight different Grhl-dependent mechanisms that modulate epithelial differentiation in the kidney. Additionally, we discuss how disruptions in these mechanisms result in impaired renal function later in life.

BACKGROUND While adult hemodialysis (HD) patients have increased morbidity with higher target hemoglobin levels, similar findings have not been demonstrated in pediatric patients. We evaluated changes in transfusions, anemia frequency, and erythropoietin (epo) dosing among pediatric HD patients before, during, and after implementation of federal dialysis payment policies regarding epo dosing for adult HD patients. METHODS This is a retrospective cohort study of pediatric HD patients enrolled in NAPRTCS. We evaluated need for transfusion, anemia, median hemoglobin, and median epo dose 6 months after starting HD in 3 eras: baseline (2003-2007), implementation (2008-2011), and post implementation (2012-2016). We used multivariate logistic regression models to evaluate potential differences in transfusion across the eras. RESULTS Six months after dialysis initiation, 12.6% of patients required transfusion pre-implementation, 17.9% during implementation, and 15.5% post implementation. Anemia occurred in 17.4% of patients pre, 23.5% during, and 23.8% post implementation, with median hemoglobin levels of 11.9 g/dL pre, 11 g/dL during, and 11 g/dL post implementation. Epo use was high across all 3 eras, but epo dosing decreased during and post implementation, despite more anemia during these periods. Odds of transfusion in implementation era compared with pre-implementation was 1.75 (95% CI 1.11-2.77) and odds of transfusion in post implementation era compared with pre was 1.19 (95% CI 0.71-1.98), controlling for age, race, gender, and prior transplant status. CONCLUSIONS During and following implementation of adult epo dosing guidelines, transfusion and anemia frequency increased in pediatric HD patients. Ideal target hemoglobin levels for pediatric dialysis patients warrant further study.