Kidney360最新文献

Background: Sodium zirconium cyclosilicate (SZC) and patiromer (PAT) are potassium binders that differ by exchange ion, sodium, and calcium, respectively. There is limited data on whether using sodium exchange could impact the risks of hospitalizations for heart failure (HHF) or severe edema in patients with hyperkalemia.

Objectives: To assess the occurrence rates of pre-specified major encounters potentially related to electrolyte-/fluid-related imbalances (including HHF, edema) among new users of PAT or SZC.

Methods: Using Cerner Real World Data, we conducted a retrospective cohort study among adults (≥18 years) who were newly initiated on SZC or PAT between June 1, 2018, and December 31, 2021. Based on baseline demographic and clinical characteristics, 1 PAT initiator was propensity score matched with 2 SZC initiators. Primary outcomes were any HHF, primary HHF, major edema encounter (MEE), or death. Cox Proportional Hazard regression models were used to estimate the association between SZC or PAT use and each outcome in the overall population and subgroups with/without prior heart failure (HF).

Results: The final cohort included 9,929 PAT initiators matched to 19, 849 SZC initiators. Mean age was 66 years old; about 50% had a history of chronic kidney disease stages 3-5, and 34% a history of HF. Incidence rates (IR) were significantly higher in the SZC cohort when compared to the PAT cohort for all outcomes. Risks of HHF (any/primary) (adjusted Hazard ratios, HR: 1.373; 95% CI: 1.337-1.410), MEE (HR: 1.330; 95% CI: 1.298-1.363), and death (HR: 1.287; 95% CI: 1.255-1.320) were also significantly higher in the SZC cohort compared to the PAT cohort (p<0.05). These findings were consistent among subgroups with/without prior HF.

Conclusions: SZC use (vs. PAT) was associated with increased risk of pre-specified encounters potentially sodium-/fluid-related, including among patients with/without pre-existing HF.

Background: Obesity is an independent risk factor for incident and recurrent nephrolithiasis. The impact of weight loss through glucagon-like peptide 1 (GLP-1) receptor agonists and dual GLP-1/ gastric inhibitory polypeptide receptor agonists (GLP-based therapies) on nephrolithiasis is not well-understood. This study examined the changes in 24-hour urine chemistry assessing for stone risk during weight loss through GLP-based therapies.

Methods: This retrospective analysis identified adult stone formers followed at our academic institution's weight wellness clinic between September 2015 and August 2023 and included patients with at least two 24-hour urine collections for stone risk assessment. 24-hour urine parameters before and during weight loss in patients on GLP-based therapies were compared.

Results: Forty-four obese patients with nephrolithiasis experienced significant weight reduction (-6.6±7.3 kg, p<0.001) over a median 1.1 years of follow-up with GLP-based therapies. During this period, there was a significant decrease in 24-hour urine oxalate (40±16 to 32±11 mg/day, p=0.002), sulfate (21±10 to 17±9 mmol/day, p=0005), and ammonium (35±22 to 29±15 mEq/day, p=0.01). There were non-significant changes in urine calcium, citrate, uric acid, pH, phosphorus, sodium, potassium, magnesium, chloride, creatinine or total volume. Additionally, there was no statistical difference in urine supersaturation indices with respect to calcium oxalate, calcium phosphate and uric acid.

Conclusion: Our results indicate that weight loss through GLP-based therapies is not associated with pro-lithogenic changes in 24-hour urine chemistry in patients with nephrolithiasis, unlike what happens with other weight loss modalities.

Background: Multiple studies have shown that females are living donors for kidney transplantation at higher rates than males. However, the underlying reasons for this observation are not well-understood. We examined the living donor evaluation process to determine the point at which sex imbalance arises. Based on a previous study, we hypothesized that both sexes are equally likely to become approved as living donors, but females are more likely to follow through with donation.

Methods: Single institution retrospective chart review of self-referrals for living donor evaluation between 1/2009 - 12/2022. Self-referrals identified using the Organ Transplant Tracking Record database and cross referenced with billing data. Exclusion at each stage of evaluation was recorded and compared between sexes using log binomial regression; unadjusted and adjusted (for donor age, race, ethnicity, relationship to recipient, and recipient sex) risk ratios (RRs) with 95% confidence interval (CI) were determined.

Results: 1,861 self-referrals were reviewed, including 1,214 (65.2%) females and 647 (34.8%) males, resulting in 146 approvals and 125 donations (76/125, 60.8% females, 49/125 39.2% males). Adjusted RRs indicated no significant differences between sexes in completing medical and/or psychosocial workup, having medical and/or psychosocial contraindications, being approved for donation, and proceeding with donation. The top medical contraindications for both sexes were obesity, hypertension, and nephrolithiasis.

Conclusion: Female overrepresentation among living donors is likely due to the 1.9 times higher rate of self-referral for evaluation. After this point, both sexes were equally likely to complete workup, be approved, and follow through with donation. Increased efforts to engage males at the initial self-referral stage has the potential to expand access to living donor kidney transplantation.

The Hispanic population of the US is the second largest racial or ethnic group comprising 18.7% of the population. However, this population is incredibly heterogeneous differing in genetic traits, cultural upbringing, educational backgrounds, and financial status. The impact of this heterogeneity on the prevalence and outcomes of renal disease and kidney transplantation is understudied compared to non-Hispanic whites and African Americans. What is known appears to be underrecognized. This review aims to critically assess current medical literature on Hispanic individuals, focusing on etiological factors, disease progression, and outcomes related to chronic kidney disease (CKD) and kidney transplantation. By doing so, we aim to underscore key areas for further in-depth investigation.

Background: Fluid overload (FO) is common and linked to high mortality in patients undergoing peritoneal dialysis (PD). This study evaluates the impact of the time interval and frequency of FO-related hospitalizations on mortality and patient survival rates in PD patients.

Methods: Data from PD patients voluntarily registered in the Database of Peritoneal Dialysis in EXcel (DPEX) was reviewed. We included patients who started PD between January 2008 and December 2018, had a history of FO-related hospitalizations after starting PD, and were followed until December 2020 or death. We analyzed the time interval to the first FO-related hospitalization after starting PD, the number of such hospitalizations, and the cumulative FO-free time. Mortality and patient survival rates were calculated, and multiple Cox regression identified factors associated with mortality.

Results: Among 1,858 patients hospitalized due to FO, those hospitalized within 12 months of starting PD or with less than 12 months of cumulative FO-free time had high mortality rates of 38.8 and 40.3 per 100 patient-years, respectively. One-year survival rates were 70.1% for those with a time to first FO-related hospitalization within 12 months of starting PD and 68.7% for those with less than 12 months of cumulative FO-free time. Adjusted hazard ratios were 2.92 (2.31-3.69) for a cumulative FO-free time of less than 12 months, 1.53 (1.18-1.99) for a time to first FO-related hospitalization within 12 months, and 1.05 (1.03-1.07) per FO-related hospitalization.

Conclusions: The time interval to the development of FO significantly impacts mortality in patients undergoing peritoneal dialysis.

Background: AKI is an established risk factor for developing CKD. Recently, the renoprotective effect of omega-3 polyunsaturated fatty acids (ω3PUFAs) has attracted attention. This study aimed to evaluate the effect of ω3PUFAs on the transition of AKI to CKD, and to identify fatty acid active metabolites in renal tissue.

Methods: Two mice models of AKI to CKD (7-week, male) and unilateral ureteral obstruction (UUO)-induced renal fibrosis (11-week, male) were fed linseed oil, rich in ω3PUFAs (Lin group), or with soybean oil, low in ω3PUFAs (Soy group). Renal fatty acids and metabolites composition in mice were measured by liquid chromatography-mass spectrometry. Rat renal fibroblast cells (NRK-49F cells) were used for in vitro study.

Results: At day 14 after 35 min bilateral renal ischemia reperfusion (IR), significant increase in survival was observed in the Lin group compared to the Soy group. Using the 30 min bilateral renal IR model (AKI to CKD model), the Lin group showed attenuated renal tissue damage and fibrosis. In addition, the antifibrotic effect of Lin group was also observed in UUO renal fibrosis model. In the two mice models, levels of eicosapentaenoic acid (EPA) and its metabolites were significantly elevated in renal tissue of mice fed with Lin. Cultured NRK-49F incubated with EPA and its metabolites 18-hydroxyeicosapentaenoic acid (18-HEPE), 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) and 17,18-dihydroxyeicosatetraenoic acid (17,18-diHETE) displayed suppressed TGF-β1-stimulated α-smooth muscle actin protein expression. These effects were suppressed in the presence of an inhibitor of a cytochrome P450 involved in EPA metabolism. This observation suggests that the EPA metabolites have antifibrotic effects.

Conclusions: ω3PUFAs prevents AKI to CKD and renal fibrosis. Moreover, the EPA metabolites 18-HEPE, 17,18-EpETE and 17,18-diHETE were found to have antifibrotic effects.

Background: Chronic kidney disease (CKD) is a pro-inflammatory and pro-fibrotic condition and can independently alter the peritoneal membrane structure. Peritoneal dialysis (PD) results in profound alterations in the peritoneal membrane. The mechanisms contributing to the alterations of the peritoneal membrane structure in CKD milieu, along with peritoneal dialysis, are poorly understood.

Methods: Here, we show that human CKD induces peritoneal membrane thickening, fibrosis, and collagen deposition and activates the Aryl Hydrocarbon Receptor pathway (AHR) in the subperitoneal vasculature. Leveraging a novel model of peritoneal dialysis in CKD mice, we confirm these CKD-induced changes in the peritoneal membrane, which are exacerbated upon exposure to the peritoneal dialysate. Peritoneal dialysate further augmented the AHR activity in endothelial cells of peritoneal microvasculature in CKD mice.

Results: Treatment of CKD mice with an AHR inhibitor in peritoneal dialysate for two weeks resulted in a 7-fold reduction in AHR expression in the endothelial cells of sub-peritoneal capillaries, a 5-fold decrease in subperitoneal space, and a 9-fold decrease in fibrosis and collagen deposition compared to vehicle-treated CKD mice. AHR inhibition reduced inflammation, subperitoneal neovascular areas, and its downstream target, tissue factor. The AHR inhibitor treatment normalized the peritoneal dialysate-induced pro-inflammatory and profibrotic cytokines, such as IL-6, MCP1, and MIP1 levels, in CKD mice.

Conclusions: This study uncovers the activation of the AHR-cytokine axis in the endothelial cells of subperitoneal vessels in humans and mice with CKD, which is likely to prime the peritoneal membrane to peritoneal dialysate-mediated alterations. This study supports further exploration of AHR as a potential therapeutic target to preserve the structural and functional integrity of the peritoneal membrane in peritoneal dialysis.

Background: Steatotic liver disease (SLD) and chronic kidney disease (CKD) are common conditions that are strongly associated. Yet, there is a paucity of data regarding the prevalence of this overlap and the factors that may drive its occurrence.

Methods: Using the National Health and Nutrition Examination survey, we examined trends among adult participants from 2005 - 2020 that defined SLD with the Fatty Liver Index. We completed correlative analyses among adult participants from 2017 - 2020 that defined SLD based on FibroScan results. We utilized multivariable survey-weighted binomial generalized linear models to determine the factors that were associated with CKD, defined as eGFR <60 or urine albumin-creatinine-ratio >30.

Results: Among the 76,496 participants included in the trend analyses, the estimated prevalence of CKD was 15.7% (95%CI 15.2 - 16.2%) and SLD was 42.3% (95%CI 41.4 - 43.2%). As compared to those without SLD, those with SLD had a significantly higher estimated prevalence of CKD (SLD: 15.7%, 95%CI 14.9 - 16.5% v. No SLD 11.2%, 95%CI 10.7 - 11.7%). In multivariate analyses of 3,667 participants who underwent FibroScan and had SLD by Fatty Liver Index, adjusting for control and presence of DM, HTN, and HLD, compared to those with normal liver stiffness, those with moderate scarring (F2) had similar odds of CKD (1.53, 95CI 0.91-2.56), those with severe scarring (F3) had higher odds of CKD (2.28, 95CI 1.20-4.32), and those with cirrhosis had higher odds of CKD (2.21, 95CI 1.13-4.32).

Conclusions: Our findings highlight that CKD is common among patients with SLD and that higher degrees of hepatic fibrosis are associated with CKD, independent of other co-morbidities of the metabolic syndrome.

Background: Acute kidney injury (AKI) is associated with increased mortality and new or progressive chronic kidney disease (CKD). Inflammatory cells play an important role in acute organ injury. We previously demonstrated that serum IL-17A levels were significantly elevated in critically ill patients with AKI and independently associated with hospital mortality. We hypothesize that IL-17A levels are elevated in hospitalized patients with AKI at diagnosis, and sustained elevation after discharge is associated with subsequent CKD incidence or progression.

Methods: Observational convenience sampling study of hospital survivors of Stage 2 or 3 AKI and controls without AKI from the ASSESS-AKI study. Patients were classified as progression or non-progression based on a composite of CKD incidence, progression, or end-stage kidney disease. IL-17A levels were evaluated with S-Plex assay (MSD) at 0- (during hospitalization), 3- and 12-month post-discharge, and analyzed along with clinical and biomarker data up to 84 months following discharge.

Results: Among 171 AKI and 175 non-AKI participants, IL-17A levels were elevated in AKI vs. non-AKI patients at 0M, 3M and 12M timepoints (p<0.05 for all comparisons). Further, IL-17A levels were elevated in the progression vs. non-progression group at the 3- and 12-month timepoints for outcomes occurring at 3-6 months and 12-84 months, respectively (p<0.05 for both). In adjusted multivariable models, IL-17A levels were not independently associated with progression of kidney disease. IL-17A levels were positively correlated with kidney disease and immune activation biomarkers at all timepoints (p<0.001).

Conclusions: IL-17A was higher in patients with AKI vs. without AKI during hospitalization and up to 1-year post-discharge. IL-17A was higher in patients with progression of kidney disease after hospitalization but not independently associated with subsequent progression of kidney disease in fully adjusted models.