Studies have found sleeping behaviors, such as sleep duration, to be associated with kidney function and cardiovascular disease risk. However, whether short or long sleep duration is a causative ...factor for kidney function impairment has been rarely studied.
We studied data from participants aged 40-69 years in the UK Biobank prospective cohort, including 25,605 self-reporting short-duration sleep (<6 hours per 24 hours), 404,550 reporting intermediate-duration sleep (6-8 hours), and 35,659 reporting long-duration sleep (≥9 hours) in the clinical analysis. Using logistic regression analysis, we investigated the observational association between the sleep duration group and prevalent CKD stages 3-5, analyzed by logistic regression analysis. We performed Mendelian randomization (MR) analysis involving 321,260 White British individuals using genetic instruments (genetic variants linked with short- or long-duration sleep behavior as instrumental variables). We performed genetic risk score analysis as a one-sample MR and extended the finding with a two-sample MR analysis with CKD outcome information from the independent CKDGen Consortium genome-wide association study meta-analysis.
Short or long sleep duration clinically associated with higher prevalence of CKD compared with intermediate duration. The genetic risk score for short (but not long) sleep was significantly related to CKD (per unit reflecting a two-fold increase in the odds of the phenotype; adjusted odds ratio, 1.80; 95% confidence interval, 1.25 to 2.60). Two-sample MR analysis demonstrated causal effects of short sleep duration on CKD by the inverse variance weighted method, supported by causal estimates from MR-Egger regression.
These findings support an adverse effect of a short sleep duration on kidney function. Clinicians may encourage patients to avoid short-duration sleeping behavior to reduce CKD risk.
To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of ...PCP prophylaxis.
This study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose < 15 mg/day, n = 27,227 and medium dose ≥ 15 to < 30 mg/day, n = 1065, based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was > 0.1/100 person-years. Cox regression with LASSO was used for analysis.
One-year PCP IR in the low-dose group was 0.01 (95% CI 0.001-0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2-1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n = 173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1-8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR = 0.2 (0.001-2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3-71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17-226)) was lower than the number needed to harm by serious ADR (45 (15-∞)).
Incidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.
Background Renal infarction is a rare condition resulting from an acute disruption of renal blood flow, and the cause and outcome of renal infarction are not well established. Study Design Case ...series. Setting & Participants 438 patients with renal infarction in January 1993 to December 2013 at 9 hospitals in Korea were included. Renal infarction was defined by radiologic findings that included single or multiple wedge-shaped parenchymal perfusion defects in the kidney. Predictor Causes of renal infarction included cardiogenic (n = 244 55.7%), renal artery injury (n = 33 7.5%), hypercoagulable (n = 29 6.6%), and idiopathic (n = 132 30.1%) factors. Outcomes We used recurrence, acute kidney injury (AKI; defined as creatinine level increase ≥ 0.3 mg/dL within 48 hours or an increase to 150% of baseline level within 7 days during the sentinel hospitalization), new-onset estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (for >3 months after renal infarction in the absence of a history of decreased eGFR), end-stage renal disease (ESRD; receiving hemodialysis or peritoneal dialysis because of irreversible kidney damage), and mortality as outcome metrics. Results Treatment included urokinase (n = 19), heparin (n = 342), warfarin (n = 330), and antiplatelet agents (n = 157). 5% of patients died during the initial hospitalization. During the median 20.0 (range, 1-223) months of follow-up, 2.8% of patients had recurrent infarction, 20.1% of patients developed AKI, 10.9% of patients developed new-onset eGFR < 60 mL/min/1.73 m2 , and 2.1% of patients progressed to ESRD. Limitations This was a retrospective study; it cannot clearly determine the specific causal mechanism for certain patients or provide information about the causes of mortality. 16 patients were excluded from the prognostic analysis. Conclusions Cardiogenic origins were the most important causes of renal infarction. Despite aggressive treatment, renal infarction can lead to AKI, new-onset eGFR < 60 mL/min/1.73 m2 , ESRD, and death.
Background Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in ...immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear. Study Design Prospective, randomized, controlled, open-label trial. Setting & Participants Septic patients with AKI receiving CVVHDF for AKI. Intervention Conventional (40 mL/kg/h) and high (80 mL/kg/h) doses of CVVHDF for the duration of CRRT. Outcomes Patient and kidney survival at 28 and 90 days, circulating cytokine levels. Results 212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P = 0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P = 0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups. Limitations Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled. Conclusions High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.
Preeclampsia is pregnancy-specific systemic syndrome characterized by the new onset of hypertension and proteinuria after 20 weeks of gestation. Approximately 5% of pregnancies are affected by ...preeclampsia worldwide.
Although there have been many advances in the understanding of the pathophysiology of preeclampsia and the quality of obstetric care, preeclampsia is still a leading cause of maternal and fetal morbidity and mortality 1. In addition, women undergoing preeclampsia are exposed to higher long-term cardiovascular and renal outcomes 2. Aggressive screening, early diagnosis, and management are essential to reduce the instances of preeclampsia. KCI Citation Count: 0
Activation of p38 mitogen-activated protein kinase (MAPK) is associated with tissue fibrosis, and inhibition of p38 MAPK can attenuate the progression of fibrosis. We aimed to investigate whether p38 ...MAPK activity in kidney tissue confirmed by immunohistochemical staining is associated with renal tubulointerstitial fibrosis in chronic kidney disease patients with IgA nephropathy. We collected kidney biopsy specimens from 341 IgA nephropathy patients and 15 control patients to identify the clinical and histopathological factors associated with kidney tubulointerstitial fibrosis and to find an association between kidney phosphorylated p38 immunoactivity and pathological grading. In addition, we aimed to investigate whether the anti-fibrotic effect of p38 MAPK inhibition can be identified by assessing the immunostaining intensity of phosphorylated p38 in kidney tissue. A renal tubulointerstitial fibrosis model was introduced using 7-week-old C57BL/6 mice subjected to unilateral ureteral obstruction (UUO). The p38 MAPK inhibitor SB-731445 was injected intraperitoneally every day for 7 days, and changes in renal fibrosis-associated markers were investigated. Assessment of kidney biopsy specimens from IgA nephropathy patients revealed that the degree of interstitial fibrosis was significantly associated with the tissue immunoactivity of phosphorylated p38. High-grade interstitial fibrosis was associated with a low glomerular filtration rate, high proteinuria, and high-grade histopathological changes, including tubular atrophy, interstitial inflammation, and glomerular sclerosis. In a mouse UUO model, renal protein expression of COL1 and phosphorylated p38 were significantly increased, and the protein expression of COL1 and phosphorylated p38 decreased in mice administered 10 mg/kg/day p38 MAPK inhibitor. We found that kidney interstitial fibrosis is associated with increased immunoactivity of phosphorylated p38 in a UUO mouse model and in human IgA nephropathy patients and that the anti-fibrotic effect of p38 MAPK inhibition can be confirmed using immunohistochemical staining for phosphorylated p38 in kidney tissue.
Summary
Despite the lack of safety and efficacy data regarding immune checkpoint inhibitors (ICIs) for renal dysfunction, they have been approved to treat even in the patients with end-stage renal ...disease (ESRD). We report our experience with ICI administration to three ESRD patients undergoing hemodialysis. One of the patients had a partial response for several months; however, the other patients had a stable disease while undergoing dialysis. The toxicity was tolerable; however, one patient developed grade 2 pneumonitis. A literature review of other rarely reported cases of hemodialysis revealed that 10 out of 13 patients had a partial response or complete response; in addition, grade 3 or grade 4 immune-related adverse events occurred in 3 patients. ESRD combined with dialysis may not be a contraindication for the use of ICIs. ICIs can be beneficial to ESRD patients undergoing dialysis. However, caution is needed regarding immune-related adverse events. Further prospective studies involving pharmacokinetic analyses are necessary to obtain reliable safety and efficacy data.
Accurate prediction of graft survival after kidney transplant is limited by the complexity and heterogeneity of risk factors influencing allograft survival. In this study, we applied machine learning ...methods, in combination with survival statistics, to build new prediction models of graft survival that included immunological factors, as well as known recipient and donor variables. Graft survival was estimated from a retrospective analysis of the data from a multicenter cohort of 3,117 kidney transplant recipients. We evaluated the predictive power of ensemble learning algorithms (survival decision tree, bagging, random forest, and ridge and lasso) and compared outcomes to those of conventional models (decision tree and Cox regression). Using a conventional decision tree model, the 3-month serum creatinine level post-transplant (cut-off, 1.65 mg/dl) predicted a graft failure rate of 77.8% (index of concordance, 0.71). Using a survival decision tree model increased the index of concordance to 0.80, with the episode of acute rejection during the first year post-transplant being associated with a 4.27-fold increase in the risk of graft failure. Our study revealed that early acute rejection in the first year is associated with a substantially increased risk of graft failure. Machine learning methods may provide versatile and feasible tools for forecasting graft survival.
With evaluation for physical performance, measuring muscle mass is an important step in detecting sarcopenia. However, there are no methods to estimate muscle mass from blood sampling.
To develop a ...new equation to estimate total-body muscle mass with serum creatinine and cystatin C level, we designed a cross-sectional study with separate derivation and validation cohorts. Total body muscle mass and fat mass were measured using dual-energy x-ray absorptiometry (DXA) in 214 adults aged 25 to 84 years who underwent physical checkups from 2010 to 2013 in a single tertiary hospital. Serum creatinine and cystatin C levels were also examined.
Serum creatinine was correlated with muscle mass (P < .001), and serum cystatin C was correlated with body fat mass (P < .001) after adjusting glomerular filtration rate (GFR). After eliminating GFR, an equation to estimate total-body muscle mass was generated and coefficients were calculated in the derivation cohort. There was an agreement between muscle mass calculated by the novel equation and measured by DXA in both the derivation and validation cohort (P < .001, adjusted R2 = 0.829, β = 0.95, P < .001, adjusted R2 = 0.856, β = 1.03, respectively).
The new equation based on serum creatinine and cystatin C levels can be used to estimate total-body muscle mass.
Mortality is higher in patients with chronic kidney disease (CKD) than in the general population, but little information is available on CKD-related mortality that is representative of the Korean ...population. Our objective was to investigate mortality risk in Korean patients with CKD.
We identified patients with incident CKD who had not undergone dialysis or kidney transplantation between January 1, 2003 and December 31, 2007 in Korea using the database of the Korean National Health Insurance Service-National Sample Cohort, and stratified the population into the following three groups: group 1 (n = 1,473), controls; group 2 (n = 2,212), patients with diabetes or hypertension, but without CKD; and group 3 (n = 2,212), patients with CKD. We then monitored them for all-cause mortality until December 2013.
A total of 1,473 patients were included in this analysis. During the follow-up period, 941 patients in group 3 died (134 deaths/1,000 person-years) compared with 550 deaths in the group 2 (34 deaths/1,000 person-years) and 459 deaths in group 1 (30 deaths/1,000 person-years). The rate ratio for mortality rate was 4.5, and the hazard ratio for mortality was 4.88 (95% confidence interval CI, 4.36-5.47,
< 0.001) in patients in group 3 compared with age- and sex-matched controls (group 1). The rate ratio for mortality rate was 4.0, and the hazard ratio for mortality was 4.36 (95% CI, 3.92-4.85,
< 0.001) in patients in group 3 compared with patients in group 2.
In this nationally representative sample cohort, excess mortality was observed in Korean patients with incident CKD.
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