Background: This study aimed to evaluate thrombotic microangiopathy’s (TMA) incidence, risk factors, and impact on outcomes and resource use in hospitalized patients with systemic lupus erythematosus (SLE). Methods: We used the National Inpatient Sample to construct a cohort of hospitalized patients with SLE from 2003–2014. We compared clinical characteristics, in-hospital treatments, outcomes, and resource use between SLE patients with and without TMA. Results: Of 35,745 hospital admissions for SLE, TMA concurrently presented or developed in 188 (0.5%) admissions. Multivariable analysis showed that age ≥ 40 years and Hispanics were significantly associated with decreased risk of TMA, whereas Asian/Pacific Islanders and history of chronic kidney disease were significantly associated with increased risk of TMA. TMA patients required more kidney biopsy, plasmapheresis, mechanical ventilation, and renal replacement therapy. TMA was significantly associated with increased risk of in-hospital mortality and acute conditions including hemoptysis, glomerulonephritis, encephalitis/myelitis/encephalopathy, hemolytic anemia, pneumonia, urinary tract infection, sepsis, ischemic stroke, seizure, and acute kidney injury. The length of hospital stays and hospitalization cost was also significantly higher in SLE with TMA patients. Conclusion: TMA infrequently occurred in less than 1% of patients admitted for SLE, but it was significantly associated with higher morbidity, mortality, and resource use.
Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis
Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.
Hospital-Acquired Serum Ionized Calcium Derangements and Their Associations with In-Hospital Mortality
Background: The objective of this study was to report the incidence of in-hospital serum ionized calcium derangement and its impact on mortality. Methods: We included 12,599 non-dialytic adult patients hospitalized at a tertiary medical center from January 2009 to December 2013 with normal serum ionized calcium at admission and at least 2 in-hospital serum ionized calcium values. Using serum ionized calcium of 4.60–5.40 mg/dL as the normal reference range, in-hospital serum ionized calcium levels were categorized based on the presence of hypocalcemia and hypercalcemia in hospital. We performed logistic regression to assess the relationship of in-hospital serum ionized calcium derangement with mortality. Results: Fifty-four percent of patients developed new serum ionized calcium derangements: 42% had in-hospital hypocalcemia only, 4% had in-hospital hypercalcemia only, and 8% had both in-hospital hypocalcemia and hypercalcemia. In-hospital hypocalcemia only (OR 1.28; 95% CI 1.01–1.64), in-hospital hypercalcemia only (OR 1.64; 95% CI 1.02–2.68), and both in-hospital hypocalcemia and hypercalcemia (OR 1.73; 95% CI 1.14–2.62) were all significantly associated with increased in-hospital mortality, compared with persistently normal serum ionized calcium levels. Conclusions: In-hospital serum ionized calcium derangements affect more than half of hospitalized patients and are associated with increased in-hospital mortality.
Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review
Medical Sciences | October 21, 2020 | Volume: 8 | Issue: 4 | Pages: 44
Background: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. Methods: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). Results: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12–57%) after eculizumab, 42% (95% CI: 2–89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50–100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5–46%) after eculizumab, 56% (95% CI: 6–100%) after TPE, and 70% (95% CI: 24–100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0–100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7–64%) and 53% (95% CI: 28–77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. Conclusions: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.
Incidence and Impacts of Inflammatory Bowel Diseases among Kidney Transplant Recipients: A Meta-Analysis
Medical Sciences | September 16, 2020 | Volume: 8 | Issue: 3 | Pages: 39
Background: The incidence of inflammatory bowel diseases (IBD) and its significance in kidney transplant recipients is not well established. We conducted this systematic review and meta-analysis to assess the incidence of and complications from IBD in adult kidney transplant recipients. Methods: Eligible articles were searched through Ovid MEDLINE, EMBASE, and the Cochrane Library from inception through April 2020. The inclusion criteria were adult kidney transplant patients with reported IBD. Effect estimates from the individual studies were extracted and combined using the fixed-effects model when I2 ≤ 50% and random-effects model when I2 > 50%. Results: of 641 citations, a total of seven studies (n = 212) were included in the systematic review. The mean age was 46.2 +/− 6.9 years and up to 51.1% were male. The mean duration of follow-up was 57.8 +/− 16.8 months. The pooled incidence of recurrent IBD was 27.6% (95% CI, 17.7–40.5%; I2 0%) while the pooled incidence of de novo IBD was 18.8% (95% CI, 10.7–31.0%; I2 61.3%). The pooled incidence of post-transplant IBD was similar across subgroup analyses. Meta-regression analyses showed no association between the incidence of IBD and age, male sex, and follow-up duration. For post-transplant complications, the pooled incidence of post-transplant infection was 4.7% (95% CI, 0.5–33.3%; I2 73.7%). The pooled incidence of graft rejection and re-transplantation in IBD patients was 31.4% (95% CI, 14.1–56.1%; I2 76.9%) and 30.4% (95% CI, 22.6–39.5%; I2 0%). Conclusion: Recurrent and de novo IBD is common among kidney transplant recipients and may result in adverse outcomes.
Mediterranean diet and the risk of chronic kidney disease: A systematic review and meta‐analysis
AbstractObjectiveMediterranean 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.MethodsWe 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.ResultsOf 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.ConclusionAdherence 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.
SGLT2 Inhibitors and Kidney Outcomes in Patients with Chronic Kidney Disease
Journal of Clinical Medicine | August 24, 2020 | Volume: 9 | Issue: 9 | Pages: 2723
Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule—glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism. Concurrently, multiple kidney and cardiovascular outcome studies have reported remarkable advantages of SGLT2i including mortality benefits. Additionally, the superiority of combination therapies (SGLT2I along with metformin/DDP-4 Inhibitors) in treatment-naïve diabetic patients is further looked into with potential signal towards glycemic and blood pressure control. Reported promising results initiate a gateway for future research targeting kidney outcomes with combination therapies as an initial approach. In the current paper, we summarize leading cardiovascular and kidney outcome trials in patients with type 2 diabetes, the role of SGLT2i in non-diabetic proteinuric kidney disease, and the potential mechanisms of action of SGLT2i with special focus on combination therapy as an initial therapeutic approach in treatment-naïve diabetic patients.
Treatment outcomes of bumetanide continuous infusion: A systematic review and meta‐analysis
AbstractThe clinical use of continuous bumetanide infusion for acute heart failure and volume overload is common. However, there is not enough supporting evidence for the use of continuous bumetanide infusion. Thus, we conducted this systematic review and meta‐analysis aiming to describe the treatment outcomes of continuous bumetanide infusion. We searched Ovid MEDLINE, EMBASE and the Cochrane Library for eligible publications. Inclusion criteria were patients age ≥18 years with bumetanide infusion for heart failure, acute kidney injury (AKI) or volume overload. From 1564 citations, three studies (n = 94 patients) were included in the systematic review and meta‐analysis. The mean dose of bumetanide was 1.08 ± 0.43 mg/hour with a mean treatment duration of 45.09 ± 10.12 hours. Mean urine output in response to continuous bumetanide infusion was 1.88 mL/kg/hour (95% confidence interval [CI], 1.72‐2.05). The incidence of AKI with continuous bumetanide infusion was 24.7% (95% CI, 8.2‐54.6). By using Pearson's correlation coefficient, increasing doses of bumetanide were correlated with increased urine output (P = .026) and increased incidence of AKI (P < .01). There was no correlation between increasing urine output and the incidence of AKI (P = .739). In conclusion, with available evidence, continuous bumetanide infusion may be used in the treatment of acute heart failure or volume overload with close monitoring for new‐onset or worsening AKI.