The association between proton pump inhibitor use and risk of post-hospitalization acute kidney injury: a multicenter prospective matched cohort study.

BACKGROUND: Proton Pump Inhibitors (PPI) are among the most commonly used drugs to treat acid-related gastrointestinal disorders in the USA. Although PPI use has been linked to acute interstitial nephritis, the side effects of post-hospitalization acute kidney injury (AKI) and the progression of kidney disease still are controversial. We conducted a matched cohort study to examine the associations between PPI use and the side effects, especially in post-hospitalization AKI. METHODS: We investigated 340 participants from the multicenter, prospective, matched-cohort ASSESS-AKI study, which enrolled participants from December 2009 to February 2015. After the baseline index hospitalization, follow-up visits were conducted every six months, and included a collection of self-reported PPI use by participants. Post-hospitalization AKI was defined as the percentage increase from the nadir to peak inpatient SCr value was ≥ 50% and/or absolute increase ≥ 0.3 mg/dL in peak inpatient serum creatinine compared with baseline outpatient serum creatinine. We applied a zero-inflated negative binomial regression model to test the relationship between PPI use and post-hospitalization AKI. Stratified Cox proportional hazards regression models also were conducted to examine the association between PPI use and the risk of progression of kidney disease. RESULTS: After controlling for demographic variables, baseline co-morbidities and drug use histories, there was no statistically significant association between PPI use and risk of post-hospitalization AKI (risk ratio [RR], 0.91; 95% CI, 0.38 to 1.45). Stratified by AKI status at baseline, no significant relationships were confirmed between PPI use and the risk of recurrent AKI (RR, 0.85; 95% CI, 0.11 to 1.56) or incidence of AKI (RR, 1.01; 95% CI, 0.27 to 1.76). Similar non-significant results also were observed in the association between PPI use and the risk of progression of kidney diseases (Hazard Ratio [HR], 1.49; 95% CI, 0.51 to 4.36). CONCLUSION: PPI use after the index hospitalization was not a significant risk factor for post-hospitalization AKI and progression of kidney diseases, regardless of the AKI status of participants at baseline.

Semiparametric marginal methods for clustered data adjusting for informative cluster size with nonignorable zeros.

Clustered or longitudinal data are commonly encountered in clinical trials and observational studies. This type of data could be collected through a real-time monitoring scheme associated with some specific event, such as disease recurrence, hospitalization, or emergency room visit. In these contexts, the cluster size could be informative because of its potential correlation with disease status, since more frequency of observations may indicate a worsening health condition. However, for some clusters/subjects, there are no measures or relevant medical records. Under such circumstances, these clusters/subjects may have a considerably lower risk of an event occurrence or may not be susceptible to such events at all, indicating a nonignorable zero cluster size. There is a substantial body of literature using observations from those clusters with a nonzero informative cluster size only, but few works discuss informative nonignorable zero-sized clusters. To utilize the information from both event-free and event-occurring participants, we propose a weighted within-cluster-resampling (WWCR) method and its asymptotically equivalent method, dual-weighted generalized estimating equations (WWGEE) by adopting the inverse probability weighting technique. The asymptotic properties are rigorously presented theoretically. Extensive simulations and an illustrative example of the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study are performed to analyze the finite-sample behavior of our methods and to show their advantageous performance compared to the existing approaches.

Joint modeling of longitudinal data with informative cluster size adjusted for zero-inflation and a dependent terminal event.

Repeated measures are often collected in longitudinal follow-up from clinical trials and observational studies. In many situations, these measures are adherent to some specific event and are only available when it occurs; an example is serum creatinine from laboratory tests for hospitalized acute kidney injuries. The frequency of event recurrences is potentially correlated with overall health condition and hence may influence the distribution of the outcome measure of interest, leading to informative cluster size. In particular, there may be a large portion of subjects without any events, thus no longitudinal measures are available, which may be due to insusceptibility to such events or censoring before any events, and this zero-inflation nature of the data needs to be taken into account. On the other hand, there often exists a terminal event that may be correlated with the recurrent events. Previous work in this area suffered from the limitation that not all these issues were handled simultaneously. To address this deficiency, we propose a novel joint modeling approach for longitudinal data adjusting for zero-inflated and informative cluster size as well as a terminal event. A three-stage semiparametric likelihood-based approach is applied for parameter estimation and inference. Extensive simulations are conducted to evaluate the performance of our proposal. Finally, we utilize the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study for illustration.

Long COVID, a comprehensive systematic scoping review.

PURPOSE: To find out what is known from literature about Long COVID until January 30, 2021. METHODS: We undertook a four-step search with no language restriction. A preliminary search was made to identify the keywords. A search strategy of all electronic databases resulted in 66 eligible studies. A forward and backward search of the references and citations resulted in additional 54 publications. Non-English language articles were translated using Google Translate. We conducted our scoping review based on the PRISMA-ScR Checklist. RESULTS: Of 120 papers, we found only one randomized clinical trial. Of the 67 original studies, 22 were cohort, and 28 were cross-sectional studies. Of the total 120 publications, 49.1% focused on signs and symptoms, 23.3% on management, and 10.8% on pathophysiology. Ten publications focused on imaging studies. The results are also presented extensively in a narrative synthesis in separated sections (nomenclature, diagnosis, pathophysiology, risk factors, signs/symptoms, management). CONCLUSIONS: The controversies in its definition have impaired proper recognition and management. The predominant symptoms were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness.

The clinical impacts of sleep apnea on mortality and allograft function in kidney transplant patients: A meta-analysis.

BACKGROUND: Sleep apnea (SA) is common in patients with advanced chronic kidney disease. However, its prevalence and clinical significance in kidney transplant patients are unknown. OBJECTIVE: To demonstrate the clinical impacts of SA on kidney allograft and mortality from current evidence to date. MATERIALS AND METHODS: Ovid -MEDLINE, EMBASE, and the Cochrane Library were searched for eligible publications. Kidney transplant recipients aged ≥ 18 years with SA were included. The outcomes included overall mortality, graft failure, and graft loss. Graft loss was attributed by either 1) graft failure requiring renal replacement therapy (RRT)or 2) death. RESULTS: Four observational studies (n = 5,259) were included in the meta-analyses. The mean age was 49.6 ± 0.4 years. Most patients were male (58.3%) and white (82.1%). Up to 25.1% had diabetes, 15.2% had SA, and 36.8% had history of smoking. The mean body mass index was 26.9 ± 0.9 kg/m2. With the mean follow-up duration of 14.4 ± 4.2 years, the pooled adjusted odds ratios (ORs) for graft failure and mortality among kidney transplant patients with SA were 1.061 (95% CI, 0.851 - 1.322; I2 = 41.3%) and 1.044 (95% CI, 0.853 - 1.278; I2 = 0%), respectively. The pooled adjusted OR for graft loss was 0.837 (95% CI, 0.597 - 1.173; I2 = 0%). On subgroup analyses, the ORs for graft failure were similar after adjusted by study year, country, study design, sample size, ethnicity, and sex. No potential publication bias was detected. CONCLUSION: With 14-year follow-up, SA in kidney transplant patients was not associated with worsening clinical and allograft outcomes, such as graft loss, graft failure, and mortality. However, additional observational studies are needed to confirm this finding.

Body mass index and chronic kidney disease outcomes after acute kidney injury: a prospective matched cohort study.

BACKGROUND: Acute kidney injury (AKI) and obesity are independent risk factors for chronic kidney disease (CKD). This study aimed to determine if obesity modifies risk for CKD outcomes after AKI. METHODS: This prospective multisite cohort study followed adult survivors after hospitalization, with or without AKI. The primary outcome was a combined CKD event of incident CKD, progression of CKD and kidney failure, examined using time-to-event Cox proportional hazards models, adjusted for diabetes status, age, pre-existing CKD, cardiovascular disease status and intensive care unit admission, and stratified by study center. Body mass index (BMI) was added as an interaction term to examine effect modification by body size. RESULTS: The cohort included 769 participants with AKI and 769 matched controls. After median follow-up of 4.3 years, among AKI survivors, the rate of the combined CKD outcome was 84.7 per1000-person-years with BMI ≥30 kg/m2, 56.4 per 1000-person-years with BMI 25-29.9 kg/m2, and 72.6 per 1000-person-years with BMI 20-24.9 kg/m2. AKI was associated with a higher risk of combined CKD outcomes; adjusted-HR 2.43 (95%CI 1.87-3.16), with no evidence that this was modified by BMI (p for interaction = 0.3). After adjustment for competing risk of death, AKI remained associated with a higher risk of the combined CKD outcome (subdistribution-HR 2.27, 95%CI 1.76-2.92) and similarly, there was no detectable effect of BMI modifying this risk. CONCLUSIONS: In this post-hospitalization cohort, we found no evidence for obesity modifying the association between AKI and development or progression of CKD.

Efficacy of abatacept treatment for focal segmental glomerulosclerosis and minimal change disease: A systematic review of case reports, case series, and observational studies
.

INTRODUCTION: The efficacy of abatacept has been demonstrated mainly in case reports, case series, and observational studies with small sample size. With current evidence, it is premature to conclude that abatacept is an effective treatment for nephrotic syndrome. MATERIALS AND METHODS: We searched MEDLINE, SCOPUS, and Cochrane Library until December 2019 for studies including patients with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) treated with abatacept. Proteinuria recovery and remission were outcomes of interest. Presence of urinary CD80 level of B7-1 staining on kidney biopsies was also reported. RESULTS: A total of 11 studies (n = 32) were included in the systematic review. 60% of patients were male. The median age was 27.5 years (range 5.2 - 72 years). Approximately 90.6% had FSGS, while 9.4% had MCD. With median follow-up of 12 months (IQR 6.38), only 15 patients (46.9%) showed response in proteinuria reduction, and 12 patients (43.8%) achieved remission with abatacept. Serious adverse events were reported in 12.5%. Additionally, we observed that patients with positive B7-1 staining on kidney biopsies had higher odds of achieving remission with abatacept (likelihood ratio 18.25; p < 0.001). We found no significant correlation between elevated CD80 levels and remissions. CONCLUSION: The efficacy of abatacept therapy for FSGS or MCD was only 43.8%. Serious adverse effects are common. However, our study suggested that abatacept should be considered only in patients with positive B7-1 staining on kidney biopsy because these patients tend to respond to treatment.

Mediterranean diet and the risk of chronic kidney disease: A systematic review and meta-analysis.

OBJECTIVE: Mediterranean diet has been shown to be associated with lower risk of cardiovascular disease. However, its association with chronic kidney disease (CKD) remains inconclusive as the results were not consistent among population-based studies. This study aims to assess the association between Mediterranean diet adherence and CKD prevention. METHODS: We performed a systematic review and meta-analysis of studies describing the risk for CKD in community-dwelling subjects ≥18 years of age. Mediterranean diet adherence was assessed by standardized food frequency questionnaires. The search was conducted through MEDLINE, EMBASE and Cochrane Library. RESULTS: Of 168 citations, a total of nine (n = 19 151) and four studies (n = 8467) were included in the systematic review and meta-analysis, respectively. Only studies adopting Mediterranean Diet Scale (MDS) were included in the analysis. The mean score was 3.8 ± 0.3 points. With the mean follow-up duration of 20.6 ± 7.0 years, the pooled odds ratio (OR) for CKD was 0.901 (95% confidence interval [CI] 0.868-0.935) for each 1-point increment of MDS. The incidence of CKD was 0.026 events per person-year (95% CI 0.008-0.045). Moreover, male sex was associated with the incidence of CKD in an adjusted meta-regression analysis. In contrast, there was no significant association between age, black race, smoking, diabetes, hypertension estimated glomerular filtration rate and total daily energy intake vs CKD incidence. CONCLUSION: Adherence to Mediterranean diet by a 1-point increment of MDS was associated with 10% lower risk of CKD. However, there were insufficient data on patients with pre-existing CKD or dialysis.

COVID-19 and maintenance hemodialysis: a systematic scoping review of practice guidelines.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has substantially impacted the provision of medical services. During the pandemic, many medical services, including facilities providing care to patients with end stage renal disease faced challenges in safeguarding patients and staff while providing clinical care. This study aims to identify the extent, range, and nature of articles related to COVID-19 and maintenance hemodialysis to understand the research gaps and propose recommendations for future research. METHODS: Using the terms: "Dialysis" OR "RRT" OR "Renal replacement therapy" AND "SARS-COV-2" OR "COVID-19" OR "novel coronavirus" OR "2019-nCov", we performed a multi-step systematic search of the literature in the English language in Pubmed, Scopus, Embase, and Web of Science published from December 1, 2019, to May 13, 2020. Two authors separately screened the title and abstracts of the documents and ruled out irrelevant articles. We obtained a full report of the papers that met our inclusion criteria and screened the full texts. We conducted a descriptive analysis of the characteristics of the included articles and performed a narrative synthesis of the results. We conducted this scoping review in accordance with the PRISMA-ScR Checklist. RESULTS: We included 22 articles in this scoping review. Perspectives (n = 9), editorials (n = 4), and case series (n = 5) were the most common types of articles. Most articles were from Italy and the United States. Seventeen (77.3%) of the articles focused on the topic of recommendation for outpatient hemodialysis units. While many of the recommendations overlapped in several articles, there were also many unique recommendations. CONCLUSIONS: most of the articles are based on single-center experience, which spontaneously developed best practices. Many of these practices have formed the basis for policies and guidelines that will guide future prevention of infection and management of patients with End Stage Renal Disease (ESRD) and COVID-19.

Rituximab therapy for focal segmental glomerulosclerosis and minimal change disease in adults: a systematic review and meta-analysis.

BACKGROUND: Use of rituximab (RTX) for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is widely described in children. Clinical evidence in adults is limited. The objective of this study was to determine the treatment outcomes of RTX in adults with FSGS and MCD. METHODS: Ovid MEDLINE, SCOPUS, and Cochrane Database of Systematic Reviews were searched up to September 2019. Out of 699 studies, we included 16 studies describing the treatment outcomes of rituximab in adult patients with FSGS or MCD. Results were reported in remission rate and relapse rate. Serious adverse events were also reported. RESULTS: A total of 16 studies were included in our review and analysis. All studies were observational studies and included a total of 221 patients (23.1% FSGS, 76.9% MCD). Mean follow-up duration was 26.3 ± 12.8 months. From the analysis of five studies with FSGS patients (n = 51), the overall remission rate and relapse rate of RTX therapy was 53.6% (95% CI, 15.8-87.6%) and 47.3% (95% CI, 25.4-70.2%), respectively. Complete remission occurred in 42.9%. In contrast, from the analysis of 11 studies with MCD patients (n = 170), the overall remission rate and relapse rate of RTX therapy was 80.3% (95% CI, 68.5-88.5%) and 35.9% (95% CI, 25.1-48.4), respectively. Complete remission occurred in 74.7%. Subgroup analyses showed that overall remission and relapse were not different after adjusted for study year and RTX dose for both FSGS and MCD. Incidence of serious adverse events was 0.092 events/year. CONCLUSIONS: Rituximab may be considered as an additional treatment to the standard therapy for adult patients with FSGS and MCD. Remissions and relapses are similar between FSGS and MCD. Serious adverse effects of rituximab were uncommon. We encourage further randomized controlled trials to confirm the efficacy of rituximab therapy in these patients.

Causal inference with a mediated proportional hazards regression model.

The natural direct and indirect effects in causal mediation analysis with survival data having one mediator is addressed by VanderWeele (2011) [1]. He derived an approach for (1) an accelerated failure time regression model in general cases and (2) a proportional hazards regression model when the time-to-event outcome is rare. If the outcome is not rare, then VanderWeele (2011) [1] did not derive a simple closed-form expression for the log-natural direct and log-natural indirect effects for the proportional hazards regression model because the baseline cumulative hazard function does not approach zero. We develop two approaches to extend VanderWeele's approach, in which the assumption of a rare outcome is not required. We obtain the natural direct and indirect effects for specific time points through numerical integration after we calculate the cumulative baseline hazard by (1) applying the Breslow method in the Cox proportional hazards regression model to estimate the unspecified cumulative baseline hazard; (2) assuming a piecewise constant baseline hazard model, yielding a parametric model, to estimate the baseline hazard and cumulative baseline hazard. We conduct simulation studies to compare our two approaches with other methods and illustrate our two approaches by applying them to data from the ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Consortium.

Prospective Comparison of Urinary Measured Creatinine Clearance With eGFR and Cystatin C Based Cis-eGFR, Including Kinetic eGFR in the Immediate Post-transplant Period With Prompt Allograft Function.

BACKGROUND: The estimated glomerular filtration rate (eGFR) and kinetic estimated glomerular filtration rate (KeGFR) have not been compared, with urinary measured creatinine clearance (mCrCl) or serum cystatin C (CysC) eGFR, soon after kidney transplantation (KTx) with prompt primary function. This study aims to compare post-KTx, urinary mCrCl, and eGFR CysC with eGFR and KeGFR. METHODS: Post-KTx, urine was collected every 12 hours from 25 of the 34 consenting subjects to calculate mCrCl and compare with Modification of Diet in Renal Disease (MDRD)-4, Jelliffe eGFR, Cockcroft-Gault creatinine clearance (CrCl), and KeGFR by Chen and Brater formulae. Serum CysC levels were also measured in the last 14 subjects to compare with creatinine, mCrCl, and eGFR CysC. RESULTS: At 12 to 96 hours post-KTx (n = 25), mCrCl was 55.8% to 13.6% higher than MDRD-4 eGFR. The mean CysC level (n = 14) was 58% to 14% lower than creatinine for up to 3.0 days post-KTx, with higher MDRD-4 eGFR CysC. Chen and Brater KeGFR were significantly lower than mCrCl and eGFR (Fig 1B, Table 1). Within 3 days post-KTx, a 50% decrease in creatinine provided ≥ 50 mL/min CrCl in 90% of cases (mean mCrCl 61.7 ± 22.8). This difference was greater when the initial creatinine was higher with the rapid decrease in creatinine. CONCLUSIONS: (1) Post-KTx eGFR/KeGFR formulae underestimated mCrCl. (2) Serum CysC levels were lower than creatinine, corresponding with higher eGFR CysC. (3) A 50% decrease from initial serum creatinine; mean mCrCl was 61.7 ± 22.8 mL/min, and 90% of them have mCrCl > 50 mL/min. Post-KTx, until creatinine is stabilized, recipients are often receiving subtherapeutic dosing of renally adjusted medications. More prospective studies are necessary, including radioisotope clearance.

A rare case of non-lupus full house nephropathy in a transplanted kidney, case report.

Key Clinical Message: Non-lupus full house nephropathy is a rare entity that is still poorly understood. It can complicate post-transplant kidneys and result in a de novo process. Treatment is difficult but can be possibly achieved with optimization of immune suppression. Abstract: Non-lupus full house nephropathy is a rare entity with an unclear incidence. It describes the kidney biopsy findings of positive deposits for IgG, IgA, IgM, C3, and C1q on immunofluorescence in the absence of the classical diagnostic features of systemic lupus nephritis. This disease entity is becoming more recognized but further studies are still needed to evaluate the incidence, etiologies, and management of this condition. Transplant glomerulopathy is a major cause for renal graft loss. It can present with a wide variety of manifestations; it can cause AKI, CKD, or glomerular inflammations through an immune complex or autoimmune-mediated damage.

Effects of ACE inhibitor/ARB therapy and long COVID on kidney disease: a retrospective cohort study using real-world data.

Background: The association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and severe acute respiratory syndrome coronavirus 2 susceptibility, particularly via ACE-2 receptor upregulation in the kidneys, raises concerns about potential kidney disease risks in long coronavirus disease (COVID) patients. This study explores the association of ACEI/ARB therapy on acute kidney injury (AKI), chronic kidney disease (CKD) and all-cause mortality in patients with and without long COVID. Methods: A retrospective cohort study using TriNetX datasets was conducted, with diagnoses of long COVID via International Classification of Diseases, Tenth Revision (ICD-10) codes and prescription for ACEI/ARB as the classification of four cohorts: long COVID ACEI/ARB users (LCAUs), long COVID ACEI/ARB non-users (LCANs), non-long COVID ACEI/ARB users (NLCAUs) and non-long COVID ACEI/ARB non-users (NLCANs). Multivariable stratified Cox proportional hazards regression models assessed the adjusted hazard ratios (aHRs) across groups. Additional analyses were conducted, including time-dependent exposure analysis and comparison with an active comparator, calcium channel blockers. Results: Our study included 18 168 long COVID and 181 680 propensity score-matched non-long COVID patients from October 2021 to October 2023. ACEI/ARB use did not significantly affect the risk of AKI or CKD when comparing LCAUs with LCANs and NLCAUs with NLCANs. However, a protective effect against all-cause mortality was observed {aHR 0.79 [95% confidence interval (CI) 0.65-0.93]} in the NLCAU group compared with the NLCAN group. Conversely, long COVID was associated with increased risks of CKD [aHR 1.49 (95% CI 1.03-2.14)] and all-cause mortality [aHR 1.49 (95% CI 1.00-2.23)] when comparing LCANs with NLCANs. The additional analyses support the primary findings. Conclusions: ACEI/ARB treatment does not increase the incidence of CKD or AKI, regardless of long COVID status. However, long COVID itself is associated with increasing risks of kidney diseases and all-cause mortality.

International survey of nephrologists' perceptions and attitudes about rewards and compensations for kidney donation.

BACKGROUND: Payment for organ donation, whether in the form of incentives, rewards or compensation is highly debated and has been denounced by many professional and legislative bodies. Despite the passionate discussion in the literature, there is very limited data on attitudes and perceptions of physicians about providing rewards or compensation to organ donors. We investigated the relationship between demographic and practice characteristics of nephrologists and their perceptions and attitudes about rewards and compensations for organ donation. METHODS: Using a web-based survey, we explored the views of nephrologists around the world about rewards and compensations for kidney donation. The relationship between attitudes and demographic characteristics of 1280 nephrologists from 74 countries was examined by univariate and multivariable analyses. RESULTS: Seventy-five percent agreed with donor health insurance, 26% favored direct financial compensation and 31% agreed with financial rewards for unrelated donors. Sixty-six percent believed that rewards will lead to increased donation. Seventy-three percent indicated that rewards will lead to exploitation of the poor and 78% agreed with legislation prohibiting organ sales. Thirty-seven percent believed that rewards will negatively impact deceased-donor transplantation. Nephrologists from India/Pakistan and the Middle East had more favorable views about rewards, while respondents from Latin America and Europe, older than 50, female nephrologists and those practicing in rural areas had less favorable views. CONCLUSIONS: We conclude that a minority of nephrologists favor rewards for donation, many agree with some compensation and a considerable majority favor donor health insurance. Perceptions of nephrologists about rewards and compensation are influenced by age, sex, urban versus rural location and geographic region of practice.

Inequity and disparities mar existing global research evidence on Long COVID.

Since the pandemic began in December 2019, SARS-Cov2 has accentuated the wide gap and disparities in socioeconomic and healthcare access at individual, community, country, and regional levels. More than two years into the current pandemic, up to three-fourths of the patients are reporting continued signs and symptoms beyond the acute phase of COVID-19, and Long COVID portends to be a major challenge in the future ahead. With a comprehensive overview of the literature, we found that most studies concerning long COVID came from high and upper-middle income countries, and people of low-income and lower-and-middle income regions and vulnerable groups with comorbid conditions have been neglected. Apart from the level of income, there is a significant geographical heterogeneity in investigating the Post-Acute Sequelae of COVID-19 (PASC) or what we call now, long COVID. We believe that these recognizing health disparities is crucial from equity perspective and is the first step toward global health promotion.

Incentives for organ donation: proposed standards for an internationally acceptable system.

Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered.

Zinc and Kidney Disease: A Review.

Zinc is the second most abundant essential trace element in the human body with important regulatory functions in cellular and subcellular levels in several tissues. Zinc deficiency is associated with the development and progression of chronic kidney disease (CKD) and its complications. With the progression of CKD to end-stage kidney disease (ESKD) and initiation of dialysis, zinc is further removed from the body, potentiating the zinc deficiency. Dietary intake plays a major role in zinc-deficiency-related risks and progression of CKD. By taking into account the evidence from clinical studies depicting the mutual correlations between zinc and CKD, and the plausibility based on animal studies, it can be deduced that zinc deficiency has a causative role in CKD and its progression. This review highlights the role of zinc deficiency in kidney disease and the possible indication for supplementation of zinc at various stages of CKD.  DOI: 10.52547/ijkd.6702.

Improving Caregiver Burden by a Peer-Led Mentoring Program for Caregivers of Patients With Chronic Kidney Disease: Randomized Controlled Trial.

Chronic kidney disease (CKD) is associated with substantial morbidity, mortality, cost, and increased caregiver burden. Peer mentoring (PM) improves multiple outcomes in various chronic diseases. The effect of PM on caregiver burden among caregivers of patients with CKD has not been studied. We conducted a randomized clinical trial to test the effectiveness of a structured PM program on burden of care among caregivers of patients with CKD. We randomized 86 caregivers to receive 6 months of intervention in 1 of 3 groups: (1) face-to-face PM (n = 29); (2) online PM (n = 29); and (3) usual care: textbook-only (n = 28). Peer mentors were caregivers of patients with CKD, who received 16 h of instruction. All participants received a copy of a textbook, which contains detailed information about kidney disease. Participants in the PM groups received FTF or online PM for 6 months. The outcome was time-related change in the Zarit Burden Interview (ZBI) score. There was a statistically significant decrease in the ZBI score (SE: -3.44; CI: -6.31, -0.57 [p = 0.002]) compared with baseline, among the online PM group. Online PM led to decreased caregiver burden among caregivers of patients with CKD. The study was limited to English-speaking subjects with computer literacy.

Considerations in Controlling for Urine Concentration for Biomarkers of Kidney Disease Progression After Acute Kidney Injury.

Introduction: Biomarkers of acute kidney injury (AKI) are often indexed to urine creatinine (UCr) or urine osmolarity (UOsm) to control for urine concentration. We evaluated how these approaches affect the biomarker-outcome association in patients with AKI. Methods: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Study was a cohort of hospitalized patients with and without AKI between 2009 and 2015. Using Cox proportional hazards regression, we assessed the associations and predictions (C-statistics) of urine biomarkers with a composite outcome of incident chronic kidney disease (CKD) and CKD progression. We used 4 approaches to account for urine concentration: indexing and adjusting for UCr and UOsm. Results: Among 1538 participants, 769 (50%) had AKI and 300 (19.5%) developed composite CKD outcome at median follow-up of 4.7 years. UCr and UOsm during hospitalization were inversely associated with the composite CKD outcome. The associations and predictions with CKD were significantly strengthened after indexing or adjusting for UCr or UOsm for urine kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) in patients with AKI. There was no significant improvement with indexing or adjusting UCr or UOsm for albumin, neutrophil gelatinase-associated lipocalin (NGAL), and chitinase 3-like 1 (YKL-40). Uromodulin's (UMOD) inverse association with the outcome was significantly blunted after indexing but not adjusting for UCr or UOsm. Conclusion: UCr and UOsm during hospitalization are inversely associated with development and progression of CKD. Indexing or adjusting for UCr or UOsm strengthened associations and improved predictions for CKD for only some biomarkers. Incorporating urinary concentration should be individualized for each biomarker in research and clinical applications.