Kidney360最新文献

Background: 'Life Years from Transplant' (LYFT) is a measure of the predicted difference between the expected lifespan with and without a kidney transplant. The metric was originally proposed in 1999; since then, demographics of the kidney transplant candidate population have materially changed.

Methods: Using contemporary SRTR data, we propose more sophisticated methods for estimating LYFT with a focus on older kidney transplant candidates, a growing sector of the current candidate pool. We examine trends in predicted LYFT from 1995 to 2020.

Results: We show that among older patients on the deceased donor waitlist, transplant remains a better option compared with dialysis (overall LYFT=5 years). LYFT trends have diminished modestly (by <1 life year) over time, in part related to efforts to enhance access to transplantation through intercurrent policy changes.

Conclusions: Updated LYFT estimates remain informative clinical measures that can support patient-centered decision making. However less homogenous metrics with meaningful disaggregation are needed to inform institutional evaluation and policy change. Models should be repeatedly evaluated as demographics of the candidate pool evolve.

Background: Individuals with end-stage renal disease may be at increased risk of sudden cardiac arrest (SCA) associated with dialysis therapy. However, community-based studies with comprehensive adjudication of SCA are lacking.

Methods: We conducted a community-based study using a case-case study design in a US population of ≈1 million. All SCA cases with chronic kidney disease (CKD) were ascertained prospectively (2002-2020). We reviewed EMS narratives and archived medical records from regional hospitals to capture patients dialysis history, schedules, and the timing of SCA events in relation to dialysis sessions. Among those on regular hemodialysis, individuals who suffered SCA during hemodialysis or within an hour after completing hemodialysis (Intradialytic/immediate post-HD [IIHD]) were compared to cases with SCA at other times (non-IIHD). Non-compliant individuals or those intolerant of dialysis were excluded.

Results: Out of 1,023 SCA cases with CKD, 195 (19.1%) were undergoing regular scheduled hemodialysis. Among these cases, 24.1% were IIHD SCA, while 75.9% occurred non-IIHD. The incidence of SCA during dialysis was 2.9 times higher than expected by chance. SCA events were more likely to occur on dialysis days (65.3% of events) vs. 34.7% events on the 4 off dialysis days (p<0.001). IIHD SCA had higher serum sodium (138.9±4.8 vs. 135.5±5.5 mmol/L, p=0.005), lower serum potassium (3.6±0.7 vs. 5.6±1.6 mmol/L, p<0.001), and higher bicarbonate levels (25.9±6.6 vs. 20.2±5.5 mmol/L, p<0.001) compared to their non-IIHD SCA counterparts. Regarding resuscitation details, IIHD SCA had a higher percentage of shockable rhythm (46.5 vs. 32.4%, p=0.09), witnessed collapse (85.1 vs. 53.4%, p<0.001), bystander CPR (72.3 vs. 37.9%, p<0.001), return of spontaneous circulation (66.0 vs. 42.5%, p=0.005), and survival to hospital discharge (30.4 vs. 5.4%, p<0.001) compared to non-IIHD SCA.

Conclusions: In patients undergoing dialysis, SCA events were significantly more common on dialysis days, and 3-fold higher than expected by chance. We identified potential risk factors and survival outcome differences between IIHD vs. non-IIHD SCA groups that warrant future investigation.

Background: Glucocorticoids are central to vasculitis treatment but increase vertebral fracture risk. This study assessed whether vasculitis as the cause of ESRD is associated with incident vertebral fracture, controlling for corticosteroid use.

Methods: A retrospective cohort study was conducted from 2006-2019 on adults in the U.S. Renal Data System initiating dialysis between 2006 and 2017, surviving ≥1 year, with continuous Medicare Part D coverage during the first year of dialysis. Primary exposure was vasculitis as the cause of ESRD determined from form Centers for Medicare & Medicaid Services (CMS)-2728, completed by a physician at dialysis initiation. A granulomatosis with polyangiitis (GPA) subgroup had ≥1 International Classification of Diseases (ICD)-9/10 code for GPA in the first dialysis year. One inpatient or two outpatient ICD-9/10 codes within 90 days defined incident vertebral fracture. Clinical covariates were ascertained from form CMS-2728 and ICD-9/10 codes and pharmacy claims over the first dialysis year. Multivariable logistic regression examined the association of ESRD secondary to vasculitis with incident vertebral fracture, and in GPA in a secondary analysis.

Results: Among 633,543 individuals with ESRD, vertebral fracture occurred in 6.18% with and 3.23% without ESRD from vasculitis. After multivariable adjustment including corticosteroid daily dose in the first dialysis year, ESRD secondary to vasculitis was associated with vertebral fracture (relative risk (RR):1.33, 95% confidence interval (CI):1.17-1.52), and similarly in those with GPA (RR:1.47, 95% CI:1.23-1.75).

Conclusions: ESRD from vasculitis, and from GPA specifically, increases vertebral fracture risk among individuals with ESRD after accounting for first dialysis year corticosteroid dose.

Background: Patient involvement in research can help to ensure that the evidence generated aligns with their needs and priorities. In the Establishing Meaningful Patient-Centered Outcomes With Relevance for Patients with Polycystic Kidney Disease (EMPOWER PKD) project we aimed to identify patient-important outcomes and discuss the impact of PKD on patients.

Methods: Nine focus groups were held with adult patients with PKD, caregivers, and clinical or research experts in PKD. We used a nominal, multi-vote technique to rank patient-important outcomes to be prioritized by future PKD research. We conducted a thematic analysis of verbatim transcriptions to identify themes regarding the impact of PKD on their daily lives. Other focus group topics included insurability and patient engagement.

Results: Ninety patients and/or caregivers and eight clinicians and/or researchers participated in the focus groups. Nine focus groups yielded 35 outcomes important to patients which were grouped into six categories, ranked in order of importance: kidney health, comorbidities, lifestyle, psychological impact, family and awareness, and mortality. Regarding the impact of PKD on the patient's daily lives, we identified 5 themes, listed in order of importance: psychological impact, effect on daily living, issues affecting decision-making, healthcare-related issues, and PKD-specific testing dilemmas.

Conclusions: This study of stakeholder engagement in patients with PKD revealed important priorities and values that should be considered for future research and when caring for patients with PKD. Future research should focus on kidney health and managing comorbidities in patients with PKD. This will help to bridge the knowledge gap and develop meaningful comparative effectiveness research (CER) in PKD.

Background: Acute kidney disease (AKD) includes abnormalities of kidney function present for <90 days. Acute kidney injury (AKI) is defined as a subset of AKD, with onset within seven days. There is scant data on the rates of AKD in children and its association with outcomes. Our primary objective was to examine the rates of AKD with and without AKI and compare major adverse events (MAKE) in children in the pediatric intensive care unit (PICU).

Methods: This is a retrospective cohort study of patients ≤18 years old who were admitted to a quaternary care PICU between 2009 and 2016 using the high-density pediatric database. All patients included in the primary analysis had a known baseline serum creatinine. Patients who had a baseline estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or a history of dialysis dependence or kidney transplant were excluded. AKI and AKD were defined by Kidney Disease: Improving Global Outcomes definitions. MAKE-90 was defined as a composite outcome of death, dialysis, or persistent kidney dysfunction 90 days after PICU admission.

Results: Among 5,922 children included in this study, 1,199 (20.2%) had AKD, of which 1,092 (91%) had AKD with AKI and 107 (8.9%) had AKD without AKI. MAKE-90 occurred in 26% (308/1,199) of those with AKD compared to 3.6% (172/4723) without (p=<0.001). MAKE-90 occurred in 26% (279/1,092) of AKD with AKI and 27% (29/107) of AKD without AKI. After adjusting for age, sex, and illness severity, compared to patients that had no AKD, patients with AKD with AKI (aOR: 14.39, 95% CI: 11.06-18.72) and patients with AKD without AKI (aOR: 7.83, 95% CI: 4.54-13.51) had a greater odds of MAKE-90.

Conclusions: More than a quarter of pediatric critically ill patients with AKD develop MAKE-90. Even in the absence of AKI, AKD is an independent risk factor for MAKE-90.

Background: The beneficial impact of peritoneal dialysis (PD) catheter placement following cardiopulmonary bypass in young infants has been demonstrated. But the indications to start early peritoneal dialysis are not agreed upon.

Methods: This retrospective single center study was conducted to evaluate the performance of a clinical strategy for early PD start. PD catheters were placed in the operating room (OR) following cardiopulmonary bypass (CPB). Those with prolonged CPB times (>180 minutes), post-operative (post-op) oligo-anuria and/or inability to achieve negative fluid balance in post-op 24 hours were evaluated as high-risk and selected for early PD start (PD +). All PD + were started within the first post-op 24 hours. Primary outcomes were 5% fluid accumulation at post-op 48 hours and severe acute kidney injury (AKI) at post-op day 5.

Results: There were forty-nine newborns. Twenty-nine subjects were early PD (PD +) starts and twenty used the PD catheter as an abdominal drain (PD -). Baseline demographic data were similar. Both groups were oliguric during post-op first 8 hours (p= 0.906). The Early PD (+) group produced significantly less urine output during post-op day 1 (0.98 vs 3.02 ml/kg/hour; p= 0.001). At post-op 48 hours, early PD (+) group had similar prevalence of 5% fluid accumulation as early PD (-), 5 (16.7%) vs. 2 (7.41%), respectively (p= 0.427). Severe AKI incidence at post-op day 5 was similar between the groups (17.3% vs 5.0%; p=0.204). Time to extubation was longer for early PD (+) group compared to PD (-) group, 10.0 days [7.0;16.0] vs. 4.0 days [4.0;10.0] (p=0.017).

Conclusions: Persistent oliguria and inability to achieve negative fluid balance during initial post-op 24 hours may identify those newborns who will benefit from early PD. The first post-operative 8 hours was indiscriminative for this strategy. PD start may ameliorate the disadvantage for the designated group.

Background: Epidemiological associations between kidney stone disease (KSD) and gastrointestinal disorders have been reported, and intestinal homeostasis plays a critical role in stone formation. However, the underlying intrinsic link is not adequately understood. This study aims to investigate the genetic associations between these two types of diseases.

Methods: We obtained summary statistics from large-scale genome-wide association studies of KSD and gastrointestinal diseases, including gastroesophageal reflux disease (GERD), peptic ulcer disease, inflammatory bowel disease and its subtypes, irritable bowel syndrome (IBS) and diverticular disease (N = 311,254 to 720,199). Their overall genetic correlations were first estimated. We then detected the shared genetic architecture, including pleiotropic single nucleotide polymorphisms (SNPs), loci, genes and biological processes, through cross-trait analyses. In addition, bidirectional Mendelian randomization (MR) analysis was performed to look for their causal relationships.

Results: We found significantly positive genetic correlations between KSD and all five gastrointestinal diseases. The cross-trait analysis identified 3184 potential pleiotropic SNPs, and 33 of which were pleiotropic loci shared by the two disorders. Gene-level analyses revealed 8 pleiotropic causal genes, primarily enriched in biological pathways involving ion homeostasis and response to vitamin D. In the MR analysis, we detected causal effects from GERD, IBS and Crohn's disease to KSD, while no reverse causality was observed.

Conclusions: Our study demonstrated the positive genetic links between KSD and gastrointestinal diseases and reported pleiotropic variants, loci, and genes, implicating potential biological mechanisms in the pathogenesis of stone disease. These findings further support the role of the gut-kidney axis and provide a genetic basis for the prevention, coregulation and treatment of these diseases.

Background: Epidermal growth factor is expressed in the distal tubule and secreted in urine (uEGF) after cleavage of membrane-bound pro-EGF. Lower uEGF is associated with kidney disease progression. EGF also plays a role in the regulation of serum magnesium and blood pressure, but whether uEGF is associated with these parameters is unknown. We hypothesized that uEGF is a distal tubule marker associated with serum magnesium, blood pressure, and kidney outcomes.

Methods: We first used a cohort of kidney donors (n = 20) and measured uEGF to analyze the association with tubular mass and pro-EGF in urinary extracellular vesicles as proxy for tubular expression. Next, we measured uEGF in a population-based cohort (n = 2382) to investigate the associations with serum magnesium, hypertension, and kidney outcomes (incident eGFR < 60 or < 45 ml/min/1.73 m2, 40% loss of eGFR or kidney failure).

Results: Kidney donation decreased eGFR from 86 to 54 ml/min/1.73 m2 (36% reduction, 95%CI 31-42%), uEGF from 28 to 14 µg/24h (49% reduction, 95%CI 42-55%) and pro-EFG by 29% (95%CI 12-45%). The decrease in uEGF correlated with the decrease in kidney volume. In the population cohort, lower uEGF was significantly associated with hypertension and lower serum magnesium. The association between uEGF and serum magnesium was stronger in participants with lower eGFR, hypertension and diuretic use. Lower uEGF at baseline was also associated with worse kidney outcomes and this association was stronger for normotensive participants.

Conclusions: uEGF is a marker of distal tubular mass that is not only associated with kidney disease progression, but also with serum magnesium and blood pressure. Future studies should address if normotensive people with low urinary EGF excretion represent a group that may benefit from kidney-protective treatment.

Background: Individuals with autosomal dominant polycystic kidney disease (ADPKD) face mental health challenges linked to disease progression and its heritable nature. Prior studies reported mixed associations between depressive symptoms and ADPKD severity and progression. Here, we assessed depressive symptoms and disease severity over three years in ADPKD patients without end-stage kidney disease.

Methods: 283 adults with ADPKD were enrolled from April 2013 to June 2023 in a single-center prospective observational study. ADPKD severity was assessed with estimated GFR and htTKV. Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II). Depressive symptom burden was compared to previously reported cohorts of patients with other chronic, progressive diseases. The relationship of ADPKD severity and ADPKD-related pain with depressive symptoms was estimated using multiple linear regression, adjusting for potential confounders.

Results: Among 283 adult ADPKD patients(mean age 45; 81% White; 61% female), 15.5% reported moderate depressive symptoms (BDI-II ≥ 11). Depressive symptom prevalence (all ages) was lower than in primary care samples. For the older individuals in our cohort, depressive symptom prevalence was similar to those in healthy older adults. ADPKD severity [eGFR: 73±33 ml/min/1.73m2, htTKV: 1104±80 cc/meter] was unrelated to depressive symptoms, although frequent pain (abdominal, back, and/or flank pain experienced at least daily) strongly associated with higher depressive symptom levels. Baseline depressive symptoms did not predict kidney function (eGFR, htTKV) at 36 months, adjusting for baseline measures and confounders.

Conclusions: Our results reveal a relatively low prevalence of clinically significant depressive symptoms in a large sample of adult patients with ADPKD who were not undergoing renal replacement therapy. However, frequent pain was associated with a greater degree of depressive symptoms, underscoring the importance of adequate pain control. While these findings highlight the resilience of patients with ADPKD, routine mental health screening is recommended, and validated pain assessment tools may provide useful resources to quantify and manage pain in ADPKD.

Background: Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. Like other types of glomerulonephritis, podocyte injury has been observed in patients with LN. However, the association between podocyte injury and kidney prognosis in patients with LN has not been well elucidated. This study aimed to explore the association between podocyte injury and clinical and histological status and kidney prognosis in patients with LN.

Methods: Seventy-five patients histopathologically diagnosed with LN were enrolled in this study. Early growth response 1 (EGR1) expression in podocytes, representing podocyte injury, was detected through immunohistochemistry. The correlation between the proportion of glomeruli with podocytes expressing EGR1 (%EGR1glo) and the clinical and histological features of LN was evaluated. Subsequently, the association between %EGR1glo and kidney prognosis was examined in a group of patients with LN classes III, IV, or V who showed ≥ 0.5 g/g of urinary protein-to-creatinine ratio (UPCR) and received immunosuppressive therapy. Hazard ratio was calculated using univariate Cox proportional hazards regression.

Results: %EGR1glo was highest in patients with LN class IV, significantly correlated with Systemic Lupus Erythematosus Disease Activity Index score, urinary protein level, and the prevalence of glomeruli showing cellular/fibrocellular crescents, endocapillary hypercellularity, and fibrinoid necrosis, and inversely correlated with eGFR. Higher %EGR1glo was significantly associated with sustained ≥ 30% eGFR decline over 10 years in patients with LN classes III, IV, or V (n = 42) (hazard ratio, 1.58 [95% confidence interval, 1.07-2.36] per 10% increase in %EGR1glo). There was no significant interaction between patients grouped by kidney function, urinary proteinuria level, presence of cellular/fibrocellular crescents, degree of tubulointerstitial fibrosis, and LN classification.

Conclusions: Podocyte damage, as indicated by EGR1 expression, was associated with poor long-term kidney prognosis in patients with active LN. Treatment strategies based on the extent of podocyte injury may be necessary.