Onconephrology: The intersections between the kidney and cancer.

Onconephrology is a new subspecialty of nephrology that recognizes the important intersections of kidney disease with cancer. This intersection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, paraneoplastic glomerulonephritis, and the interactions of chronic kidney disease with cancer. Data clearly demonstrate that, when patients with cancer develop acute or chronic kidney disease, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. This highlights the imperative for collaborative care between oncologists and nephrologists in recognizing and treating kidney disease in patients with cancer. In response to this need, specific training programs in onconephrology as well as dedicated onconephrology clinics have appeared. This comprehensive review covers many of the critical topics in onconephrology, with a focus on acute kidney injury, chronic kidney disease, drug-induced nephrotoxicity, kidney disease in stem cell transplantation, and electrolyte disorders in patients with cancer.

Probiotic use in pediatric kidney transplant recipients: What are current practices, and are they evidence-based? A pediatric nephrology research consortium study.

BACKGROUND: Probiotics are living microorganisms that may confer health benefits to their host if administered in sufficient quantities. However, data on the use of probiotics in transplant recipients are scarce. METHOD: This multi-center survey of pediatric nephrologists aimed to examine variations in practice regarding the use of probiotics in pediatric kidney transplant recipients. The survey was conducted via a 10-item questionnaire (developed in Survey Monkey) administered to pediatric nephrologists participating in the Pediatric Nephrology Research Consortium meeting in April 2023. RESULTS: Sixty-four pediatric nephrologists completed the survey. Twenty-seven (42.2%) respondents reported having prescribed probiotics to pediatric kidney transplant recipients. The primary reason for probiotic use was the treatment of antibiotic-associated diarrhea (n = 20), with other reasons including recurrent Clostridium difficile infection (n = 15), general gut health promotion (n = 12), recurrent urinary tract infections (n = 8), and parental request (n = 1). Of those who prescribed probiotics, 48.1% held them during periods of neutropenia and 14.8% during central venous line use. Of the 64 respondents, 20 reported the lack of safety data as a concern for using probiotics in kidney transplant recipients. CONCLUSION: Pediatric nephrologists are increasingly prescribing probiotics to pediatric kidney transplant recipients; nevertheless, substantial practice variations exist. The paucity of safety data is a significant deterrent to probiotic use in this population.

Utilizing electronic medical records alert to improve documentation of neonatal acute kidney injury.

BACKGROUND: Neonatal acute kidney injury (AKI) is a common yet underdiagnosed condition in neonates with significant implications for long-term kidney health. Lack of timely recognition and documentation of AKI contributes to missed opportunities for nephrology consultation and follow-up, potentially leading to adverse outcomes. METHODS: We conducted a quality improvement (QI) project to address this by incorporating an automated real-time electronic medical record (EMR)-AKI alert system in the Neonatal Intensive Care Unit (NICU) at Le Bonheur Children's Hospital. Our primary objective was to improve documentation of neonatal AKI (defined as serum creatinine (SCr) > 1.5 mg/dL) by 25% compared to baseline levels. The secondary goal was to increase nephrology consultations and referrals to the neonatal nephrology clinic. We designed an EMR-AKI alert system to trigger for neonates with SCr > 1.5 mg/dL, automatically adding AKI diagnosis to the problem list. This prompted physicians to consult nephrology, refer neonates to the nephrology clinic, and consider medication adjustments. RESULTS: Our results demonstrated a significant improvement in AKI documentation after implementing the EMR-AKI alert, reaching 100% compared with 7% at baseline (p < 0.001) for neonates with SCr > 1.5 mg/dL. Although the increase in nephrology consultations was not statistically significant (p = 0.5), there was a significant increase in referrals to neonatal nephrology clinics (p = 0.005). CONCLUSIONS: Integration of an EMR alert system with automated documentation offers an efficient and economical solution for improving neonatal AKI diagnosis and documentation. This approach enhances healthcare provider engagement, streamlines workflows, and supports QI. Widespread adoption of similar approaches can lead to improved patient outcomes and documentation accuracy in neonatal AKI care.

Nephrology workforce in China: describing current status and evaluating the optimal capacity based on real-world data.

OBJECTIVE: This study aims to characterize the current status of the nephrology workforce in China and evaluate its optimal capacity based on real-world patient mobility data. METHODS: Data on nephrologists in China were collected from two prominent online healthcare platforms using web crawlers and natural language processing techniques. Hospitalization records of patients with chronic kidney disease (CKD) from January 2014 to December 2018 were extracted from a national administrative database in China. City-level paths of patient mobility were identified. Effects of nephrology workforce on patient mobility were analyzed using multivariate Poisson regression models. RESULTS: Altogether 9.13 nephrologists per million population (pmp) were in practice, with substantial city-level variations ranging from 0.16 to 88.79. The ratio of nephrologists to the estimated CKD population was 84.57 pmp. Among 6 415 559 hospitalizations of patients with CKD, 21.3% were cross-city hospitalizations and 7441 city-level paths of patient mobility with more than five hospitalizations were identified. After making adjustment for healthcare capacity, healthcare insurance, economic status, and travel characteristics, the Poisson regression models revealed that the number of nephrologists in both the source city (incidence rate ratio [IRR] 0.99, per 1 pmp increase) and destination city (IRR 1.07, per 1 pmp increase) were independently associated with patient mobility. An IRR plateau was observed when the number of nephrologists exceeded 12 pmp in the source city, while a rapidly increasing IRR was observed beyond 20 pmp in the destination city. CONCLUSIONS: The nephrology workforce in China exhibits significant geographic variations. Based on local healthcare needs, an optimal range of 12-20 nephrologists pmp is suggested.

Onco-nephrology: Physicians' Expectations About a New Subspecialty.

INTRODUCTION: Renal events are common in cancer patients and malignancy is a prevalent complication in both patients transplanted and under kidney replacement therapy (KRT). In recent years, onco-nephrology has been developed as a subspecialty whose scope has not been well established yet. The aim of our study was to assess resident and senior physicians' knowledge and expectations about onco-nephrology. METHODS AND MATERIALS: Two anonymous self-administered online questionnaires were developed by a multidisciplinary team and distributed to French residents and senior physicians. RESULTS: Two hundred twenty-eight physicians answered the survey, including 128 (56%) nephrologists, of which 98 (43%) were senior physicians and 130 (57%) were residents. Nephrologists rated their confidence in their ability to face onco-nephrological situation at 6/10 (interquartile range (IQR) 4.0-7.0) and oncologists at 6.0/10 (5.0-7.0). Managing cancer drugs in patients on KRT or in transplanted patients and discussion about introducing dialysis in cancer patients were designated as the most challenging topics. Asking if they had received appropriate learning, residents' median agreement was ranked at 3.0/10 (2.0-4.0). Forty-six percent of the respondents considered available resources as not appropriate. Specialized onco-nephrology consultations were accessible for 21% of the respondents. Finally, respondents thought there is a strong need for a national working group (8.3/10) with 87% of them expecting new reliable guidelines. CONCLUSION: The present survey revealed physicians' expectations about onco-nephrology implementation in France. An appropriate answer could be the creation of a national working group. Therefore, GRIFON (Groupe de Recherche Interdisciplinaire en OncoNéphrologie) has recently been created.

Incorporating genetics services into adult kidney disease care.

Studies have shown that as many as 1 in 10 adults with chronic kidney disease has a monogenic form of disease. However, genetic services in adult nephrology are limited. An adult Kidney Genetics Clinic was established within the nephrology division at a large urban academic medical center to increase access to genetic services and testing in adults with kidney disease. Between June 2019 and December 2021, a total of 363 patients were referred to the adult Kidney Genetics Clinic. Of those who completed genetic testing, a positive diagnostic finding was identified in 27.1%, a candidate diagnostic finding was identified in 6.7% of patients, and a nondiagnostic positive finding was identified in an additional 8.6% of patients, resulting in an overall yield of 42.4% for clinically relevant genetic findings in tested patients. A genetic diagnosis had implications for medical management, family member testing, and eligibility for clinical trials. With the utilization of telemedicine, genetic services reached a diverse geographic and patient population. Genetic education efforts were integral to the clinic's success, as they increased visibility and helped providers identify appropriate referrals. Ongoing access to genomic services will remain a fundamental component of patient care in adults with kidney disease.

Which patients with CKD will benefit from genomic sequencing? Synthesizing progress to illuminate the future.

PURPOSE OF REVIEW: This review will summarize and synthesize recent findings in regard to monogenic kidney disorders, including how that evidence is being translated into practice. It will add to existing key knowledge to provide context for clinicians in consolidating existing practice and approaches. RECENT FINDINGS: Whilst there are long established factors, which indicate increased likelihood of identifying a monogenic cause for kidney disease, these can now be framed in terms of the identification of new genes, new indications for genomic testing and new evidence for clinical utility of genomic testing in nephrology. Further, inherent in the use of genomics in nephrology are key concepts including robust informed consent, variant interpretation and return of results. Recent findings of variants in genes related to complex or broader kidney phenotypes are emerging in addition to understanding of de novo variants. Phenocopy phenomena are indicating a more pragmatic use of broader gene panels whilst evidence is emerging of a role in unexplained kidney disease. Clinical utility is evolving but is being successfully demonstrated across multiple domains of outcome and practice. SUMMARY: We provide an updated framework of evidence to guide application of genomic testing in chronic kidney disease (CKD), building upon existing principles and knowledge to indicate how the practice and implementation of this can be applied today. There are clearly established roles for genomic testing for some patients with CKD, largely those with suspected heritable forms, with these continuing to expand as new evidence emerges.

Patient-Reported Outcomes as Endpoints in Clinical Trials of Kidney Transplantation Interventions.

Patient-reported outcomes (PROs) that assess individuals' perceptions of life participation, medication adherence, disease symptoms, and therapy side effects are extremely relevant in the context of kidney transplantation. All PROs are potentially suitable as primary or secondary endpoints in interventional trials that aim to improve outcomes for transplant recipients. Using PRO measures (PROMs) in clinical trials facilitates assessment of the patient's perspective of their health, but few measures have been developed and evaluated in kidney transplant recipients; robust methodologies, which use validated instruments and established frameworks for reporting, are essential. Establishing a core PROM for life participation in kidney transplant recipients is a critically important need, which is being developed and validated by the Standardized Outcomes in Nephrology (SONG)-Tx Initiative. Measures involving electronic medication packaging and smart technologies are gaining traction for monitoring adherence, and could provide more robust information than questionnaires, interviews, and scales. This article summarizes information on PROs and PROMs that was included in a Broad Scientific Advice request on clinical trial design and endpoints in kidney transplantation. This request was submitted to the European Medicines Agency (EMA) by the European Society for Organ Transplantation in 2016. Following modifications, the EMA provided its recommendations in late 2020.

Perspectives in systems nephrology.

Chronic kidney diseases (CKD) are a major health problem affecting approximately 10% of the world's population and posing increasing challenges to the healthcare system. While CKD encompasses a broad spectrum of pathological processes and diverse etiologies, the classification of kidney disease is currently based on clinical findings or histopathological categorizations. This descriptive classification is agnostic towards the underlying disease mechanisms and has limited progress towards the ability to predict disease prognosis and treatment responses. To gain better insight into the complex and heterogeneous disease pathophysiology of CKD, a systems biology approach can be transformative. Rather than examining one factor or pathway at a time, as in the reductionist approach, with this strategy a broad spectrum of information is integrated, including comprehensive multi-omics data, clinical phenotypic information, and clinicopathological parameters. In recent years, rapid advances in mathematical, statistical, computational, and artificial intelligence methods enable the mapping of diverse big data sets. This holistic approach aims to identify the molecular basis of CKD subtypes as well as individual determinants of disease manifestation in a given patient. The emerging mechanism-based patient stratification and disease classification will lead to improved prognostic and predictive diagnostics and the discovery of novel molecular disease-specific therapies.

Renal supportive care, palliative care and end-of-life care: Perceptions of similarities, differences and challenges across Australia and New Zealand.

Renal supportive care (RSC) is an approach integrating nephrology and palliative care to improve quality of life for people with chronic kidney disease (CKD). RSC practice varies across services; therefore, understanding clinicians' perspectives is important to the evolution and definition of RSC. AIM: To understand renal clinicians' views and experiences of RSC, palliative care and end-of-life care. METHOD: A cross-sectional online survey was undertaken across Australia and New Zealand between February and May 2018. Participants were asked about end-of-life care, RSC, palliative care and an ideal model of RSC. RESULTS: Estimated response rate 13% included 382 clinicians; doctors (32%), nurses (68%); of whom 84% access specialist palliative care and 59% RSC. A lack of agreed treatment goals (86%) and late or rushed treatment decision making (85%) was associated with challenging end-of-life experiences. Variable concepts of RSC were described, with RSC being considered the same as: usual care for all CKD patients (40%), conservative (30%) or palliative care (22%). The term RSC was generally distinct from (77%) and more acceptable than palliative care (80%) with preferential RSC referral for symptoms (86% vs 69%, P < .01) and complex treatment decision making (82% vs 58%, P < .01). Aspirations for RSC included improving symptoms and quality of life (89%), with an ideal model comprising: symptom management (98%), improved nephrology and community service integration (96%) and clinician education (94%). CONCLUSION: This study revealed challenges for renal clinicians in providing end-of-life care and variation of views and experiences of RSC. It represents opportunities to develop RSC aligned with clinician priorities to improve patient care.

[Nephrology†: what's new in 2020†?] / Néphrologie.

Impact of gliflozines in the treatment of non-diabetic nephropathies and cardiac failure has lately been demonstrated. Tolvaptan has now been recognized in Switzerland as a treatment of hyponatremia. In hemodialysis, some progress has been made in the management of dysfunctional arterio-venous fistulas. A glimmer of hope in the treatment of uremic pruritus? Conservative management of a stable coronary heart disease is also advocated in patients with end-stage kidney disease. Therapy with immune cells may either minimize or remove the need for immunosuppression in renal transplant patients. A new predictive score combining several markers can predict long-term graft failure.

L'efficacité des gliflozines est également reconnue dans le traitement de l'insuffisance cardiaque et des néphropathies non diabétiques. Le tolvaptan est maintenant reconnu en Suisse pour le traitement de l'hyponatrémie. Une stratégie de mise en dialyse plus attentiste dans l'insuffisance rénale aiguë est définitivement confirmée. En hémodialyse, quelques progrès sont obtenus dans la prise en charge des dysfonctions d'accès vasculaires et du prurit urémique. Un traitement conservateur d'emblée est préconisé pour une coronaropathie stable également chez les patients en insuffisance rénale terminale. En transplantation rénale, l'emploi d'une immunothérapie cellulaire permettrait de diminuer ou même d'arrêter l'immunosuppression. La perte du greffon peut être évaluée avec un nouveau score prédictif combinant plusieurs marqueurs.

Critical Care Nephrology: Core Curriculum 2020.

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.

Genotype-Guided Hydralazine Therapy.

BACKGROUND: Despite its approval in 1953, hydralazine hydrochloride continues to be used in the management of resistant hypertension, a condition frequently managed by nephrologists and other clinicians. Hydralazine hydrochloride undergoes metabolism by the N-acetyltransferase 2 (NAT2) enzyme. NAT2 is highly polymorphic as approximately 50% of the general population are slow acetylators. In this review, we first evaluate the link between NAT2 genotype and phenotype. We then assess the evidence available for genotype-guided therapy of hydralazine, specifically addressing associations of NAT2 acetylator status with hydralazine pharmacokinetics, antihypertensive efficacy, and toxicity. SUMMARY: There is a critical need to use hydralazine in some patients with resistant hypertension. Available evidence supports a significant link between genotype and NAT2 enzyme activity as 29 studies were identified with an overall concordance between genotype and phenotype of 92%. The literature also supports an association between acetylator status and hydralazine concentration, as fourteen of fifteen identified studies revealed significant relationships with a consistent direction of effect. Although fewer studies are available to directly link acetylator status with hydralazine antihypertensive efficacy, the evidence from this smaller set of studies is significant in 7 of 9 studies identified. Finally, 5 studies were identified which support the association of acetylator status with hydralazine-induced lupus. Clinicians should maintain vigilance when prescribing maximum doses of hydralazine. Key Messages: NAT2 slow acetylator status predicts increased hydralazine levels, which may lead to increased efficacy and adverse effects. Caution should be exercised in slow acetylators with total daily hydralazine doses of 200 mg or more. Fast acetylators are at risk for inefficacy at lower doses of hydralazine. With appropriate guidance on the usage of NAT2 genotype, clinicians can adopt a personalized approach to hydralazine dosing and prescription, enabling more efficient and safe treatment of resistant hypertension.

Assessment of Hydration Status in Peritoneal Dialysis Patients: Validity, Prognostic Value, Strengths, and Limitations of Available Techniques.

BACKGROUND: The majority of patients undergoing peritoneal dialysis (PD) suffer from volume overload and this overhydration is associated with increased mortality. Thus, optimal assessment of volume status in PD is an issue of paramount importance. Patient symptoms and physical signs are often unreliable indexes of true hydration status. SUMMARY: Over the past decades, a quest for a valid, reproducible, and easily applicable technique to assess hydration status is taking place. Among existing techniques, inferior vena cava diameter measurements with echocardiography and natriuretic peptides such as brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide were not extensively examined in PD populations; while having certain advantages, their interpretation are complicated by the underlying cardiac status and are not widely available. Bioelectrical impedance analysis (BIA) techniques are the most studied tool assessing volume overload in PD. Volume overload assessed with BIA has been associated with technique failure and increased mortality in observational studies, but the results of randomized trials on the value of BIA-based strategies to improve volume-related outcomes are contradictory. Lung ultrasound (US) is a recent technique with the ability to identify volume excess in the critical lung area. Preliminary evidence in PD showed that B-lines from lung US correlate with echocardiographic parameters but not with BIA measurements. This review presents the methods currently used to assess fluid status in PD patients and discusses existing data on their validity, applicability, limitations, and associations with intermediate and hard outcomes in this population. Key Message: No method has proved its value as an intervening tool affecting cardiovascular events, technique, and overall survival in PD patients. As BIA and lung US estimate fluid overload in different compartments of the body, they can be complementary tools for volume status assessment.

Practical application of ABPM in the pediatric nephrology clinic.

The use of 24-h ABPM has become commonplace when diagnosing and managing hypertension in the pediatric population. Multiple clinical guidelines recommend ABPM as the preferred method for identifying white-coat hypertension, masked hypertension, and determining degree of blood pressure (BP) control. Accurate, timely diagnosis and optimal management are particularly important in certain populations, such as children with chronic kidney disease (CKD), diabetes, and other conditions with increased risk for cardiovascular disease. Understanding how best to utilize ABPM to achieve these goals is important for pediatric nephrologists and other hypertension specialists. This review will provide practical information on the equipment, application, interpretation, and documentation of ABPM in the specialty clinic.

Dialysis modalities for the management of pediatric acute kidney injury.

Acute kidney injury (AKI) is an increasingly frequent complication among hospitalized children. It is associated with high morbidity and mortality, especially in neonates and children requiring dialysis. The different renal replacement therapy (RRT) options for AKI have expanded from peritoneal dialysis (PD) and intermittent hemodialysis (HD) to continuous RRT (CRRT) and hybrid modalities. Recent advances in the provision of RRT in children allow a higher standard of care for increasingly ill and young patients. In the absence of evidence indicating better survival with any dialysis method, the most appropriate dialysis choice for children with AKI is based on the patient's characteristics, on dialytic modality performance, and on the institutional resources and local practice. In this review, the available dialysis modalities for pediatric AKI will be discussed, focusing on indications, advantages, and limitations of each of them.

Energy and protein requirements for children with CKD stages 2-5 and on dialysis-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce.

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.

Nephrotoxic medications and acute kidney injury risk factors in the neonatal intensive care unit: clinical challenges for neonatologists and nephrologists.

Neonatal acute kidney injury (AKI) is common. Critically ill neonates are at risk for AKI for many reasons including the severity of their underlying illnesses, prematurity, and nephrotoxic medications. In this educational review, we highlight four clinical scenarios in which both the illness itself and the medications indicated for their treatment are risk factors for AKI: sepsis, perinatal asphyxia, patent ductus arteriosus, and necrotizing enterocolitis. We review the available evidence regarding medications commonly used in the neonatal period with known nephrotoxic potential, including gentamicin, acyclovir, indomethacin, vancomycin, piperacillin-tazobactam, and amphotericin. We aim to illustrate the complexity of decision-making involved for both neonatologists and pediatric nephrologists when managing infants with these conditions and advocate for ongoing multidisciplinary collaboration in the development of better AKI surveillance protocols and AKI mitigation strategies to improve care for these vulnerable patients.

The importance of clinician, patient and researcher collaborations in Alport syndrome.

Alport syndrome is caused by mutations in the genes COL4A3, COL4A4 or COL4A5 and is characterised by progressive glomerular disease, sensorineural hearing loss and ocular defects. Occurring in less than 1:5000, Alport syndrome is a rare genetic disorder but still accounts for > 1% of the prevalent population receiving renal replacement therapy. There is also increasing awareness about the risk of chronic kidney disease in individuals with heterozygous mutations in Alport syndrome genes. The mainstay of current therapy is the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, yet potential new therapies are now entering clinical trials. The 2017 International Workshop on Alport Syndrome in Glasgow was a pre-conference workshop ahead of the 50th anniversary meeting of the European Society for Pediatric Nephrology. It focussed on updates in clinical practice, genetics and basic science and also incorporated patient perspectives. More than 80 international experts including clinicians, geneticists, researchers from academia and industry, and patient representatives took part in panel discussions and breakout groups. This report summarises the workshop proceedings and the relevant contemporary literature. It highlights the unique clinician, patient and researcher collaborations achieved by regular engagement between the groups.

Alarm interventions for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) affects up to 20% of five-year-olds and can have considerable social, emotional and psychological effects. Treatments include alarms (activated by urination), behavioural interventions and drugs. OBJECTIVES: To assess the effects of enuresis alarms for treating enuresis in children. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, and handsearching of journals and conference proceedings (searched 25 June 2018), and reference lists of relevant articles. SELECTION CRITERIA: We included randomised or quasi-randomised trials of enuresis alarms or alarms combined with another intervention for treating nocturnal enuresis in children between 5 and 16 years old. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data. MAIN RESULTS: We included 74 trials (5983 children). At treatment completion, alarms may reduce the number of wet nights a week compared to control or no treatment (mean difference (MD) -2.68, 95% confidence interval (CI) -4.59 to -0.78; 4 trials, 127 children; low-quality evidence). Low-quality evidence suggests more children may achieve complete response (14 consecutive dry nights) with alarms compared to control or no treatment (RR 7.23, 95% CI 1.40 to 37.33; 18 trials, 827 children) and that more children may remain dry post-treatment (RR 9.67, 95% CI 4.74 to 19.76; 10 trials, 366 children; low-quality evidence). At treatment completion, we are uncertain whether there is any difference between alarms and placebo drugs in the number of wet nights a week (MD -0.96, 95% CI -2.32 to 0.41; 1 trial, 47 children; very low-quality evidence). Alarms may result in more children achieving complete response than with placebo drugs (RR 1.59, 95% CI 1.16 to 2.17; 2 trials, 181 children; low-quality evidence). No trials comparing alarms to placebo reported the number of children remaining dry post-treatment. Compared with control alarms, code-word alarms probably slightly increase the number of children achieving complete response at treatment completion (RR 1.11, 95% CI 0.97 to 1.27; 1 trial, 353 children; moderate-quality evidence) but there is probably little to no difference in the number of children remaining dry post-treatment (RR 0.91, 95% CI 0.79 to 1.05; moderate-quality evidence). Very low-quality evidence means we are uncertain if there are any differences in effectiveness between the other different types of alarm. At treatment completion, alarms may reduce the number of wet nights a week compared with behavioural interventions (waking, bladder training, dry-bed training, and star chart plus rewards) (MD -0.81, 95% CI -2.01 to 0.38; low-quality evidence) and may increase the number of children achieving complete response (RR 1.77, 95% CI 0.98 to 3.19; low-quality evidence) and may slightly increase the number of children remaining dry post-treatment (RR 1.39, 95% CI 0.81 to 2.41; low-quality evidence). The evidence relating to alarms compared with desmopressin in the number of wet nights a week (MD -0.64, 95% CI -1.77 to 0.49; 4 trials, 285 children) and the number of children achieving complete response at treatment completion (RR 1.12, 95% CI 0.93 to 1.36; 12 trials, 1168 children) is low-quality, spanning possible harms and possible benefits. Alarms probably slightly increase the number of children remaining dry post-treatment compared with desmopressin (RR 1.30, 95% CI 0.92 to 1.84; 5 trials, 565 children; moderate-quality evidence). At treatment completion, we are uncertain if there is any difference between alarms and tricyclics in the number of wet nights a week, the number of children achieving complete response or the number of children remaining dry post-treatment, because the quality of evidence is very low. Due to very low-quality evidence we are uncertain about any differences in effectiveness between alarms and cognitive behavioural therapy, psychotherapy, hypnotherapy and restricted diet. Alarm plus desmopressin may reduce the number of wet nights a week compared with desmopressin monotherapy (MD -0.88, 95% CI -0.38 to -1.38; 2 trials, 156 children; low-quality evidence). Alarm plus desmopressin may increase the number of children achieving complete response (RR 1.32, 95% CI 1.08 to 1.62; 5 trials, 359 children; low-quality evidence) and the number of children remaining dry post-treatment (RR 2.33, 95% CI 1.26 to 4.29; 2 trials, 161 children; low-quality evidence) compared with desmopressin alone. Alarm plus dry-bed training may increase the number of children achieving a complete response compared to dry-bed training alone (RR 3.79, 95% CI 1.85 to 7.77; 1 trial, 80 children; low-quality evidence). It is unclear if there is any difference in the number of children remaining dry post-treatment because of the wide confidence interval (RR 0.56, 95% CI 0.15 to 2.12; low-quality evidence). Due to very low-quality evidence, we are uncertain about any differences in effectiveness between alarm plus bladder training versus bladder training alone. Of the 74 included trials, 17 reported one or more adverse events, nine reported no adverse events and 48 did not mention adverse events. Adverse events attributed to alarms included failure to wake the child, ringing without urination, waking others, causing discomfort, frightening the child and being too difficult to use. Adverse events of comparator interventions included nose bleeds, headaches and abdominal pain. There is probably a slight increase in adverse events between code-word alarm and standard alarm (RR 1.34, 95% CI 0.75 to 2.38; moderate-quality evidence), although we are uncertain because of the wide confidence interval. Alarms probably reduce the number of children experiencing adverse events compared with desmopressin (RR 0.38, 95% CI 0.20 to 0.71; 5 trials, 565 children; moderate-quality evidence). Very low-quality evidence means we cannot be certain whether the adverse event rate for alarms is lower than for other treatments. AUTHORS' CONCLUSIONS: Alarm therapy may be more effective than no treatment in reducing enuresis in children. We are uncertain if alarm therapy is more effective than desmopressin but there is probably a lower risk of adverse events with alarms than with desmopressin. Despite the large number of trials included in this review, further adequately-powered trials with robust randomisation are still needed to determine the full effect of alarm therapy.