Association of 1,25 dihydroxyvitamin D with left ventricular hypertrophy and left ventricular diastolic dysfunction in patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.

Obesity exacerbates ischemia-reperfusion injury and senescence in murine kidneys and perirenal adipose tissues.

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

Sarcopenia is independently associated with mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

Background: Sarcopenia upon admission to the intensive care unit (ICU) consistently correlates with adverse outcomes, including heightened mortality, in critically ill patients. This study aims to investigate the independent association of sarcopenia with both mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury (SIAKI) undergoing continuous renal replacement therapy (CRRT). Methods: This retrospective study included 618 patients with SIAKI who underwent CRRT in our ICU. All patients had abdominal computed tomography (CT) scans within 3 days preceding ICU admission. The cross-sectional area of skeletal muscles at the third lumbar vertebra was quantified, and the skeletal muscle index (SMI), a normalized measure of skeletal muscle mass, was computed. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Results: Among the 618 patients, 301 expired within 28 days of ICU admission. Multivariable Cox regression analysis revealed that sarcopenia independently predicted 28-day mortality. Among survivors, sarcopenia was independently associated with recovery from dialysis within 28 days after ICU admission. Kaplan-Meier analysis illustrated that sarcopenic patients had a higher mortality rate and a lower rate of recovery from dialysis within 28 days after ICU admission compared to non-sarcopenic patients. Conclusion: This study underscores the independent association of sarcopenia, assessed via CT-derived SMI, with both mortality and recovery from dialysis in critically ill patients with SIAKI undergoing CRRT. The inclusion of sarcopenia assessment could serve as a valuable tool for physicians in effectively stratifying the risk of adverse outcomes in these patients.

Impact of nonspecific allograft biopsy findings in symptomatic kidney transplant recipients.

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.

Pre-treatment with ß-hydroxybutyrate mitigates cisplatin-induced acute kidney injury.

ß-Hydroxybutyrate (ß-HB), the primary circulating ketone body, plays a dual role as both a metabolic fuel and an endogenous signaling molecule, offering diverse systemic benefits. Recent studies have highlighted the renoprotective effects of exogenous ß-HB therapy in various animal models of kidney disease. In this investigation, our goal was to assess whether pre-treatment with exogenous ß-HB could alleviate kidney damage in a mouse model of cisplatin-induced acute kidney injury (AKI). Prior to cisplatin administration, intraperitoneal administration of ß-HB was carried out, and the groups were classified into four: Sham, ß-HB, cisplatin, and ß-HB + cisplatin. The tubular damage score and serum creatinine levels were significantly lower in the ß-HB + cisplatin group compared to the cisplatin group. Furthermore, the expression of phosphorylated NF-κB, inflammatory cytokines, and the quantity of F4/80-positive macrophages in the ß-HB + cisplatin group were reduced compared to those in the cisplatin group. Additionally, oxidative stress markers for DNA, protein, and lipid in the ß-HB + cisplatin group were markedly diminished compared to those in the cisplatin group. The number of TUNEL-positive and cleaved caspase 3-positive tubular cells in the ß-HB + cisplatin group was lower than in the cisplatin group. Pre-treating with exogenous ß-HB effectively mitigated kidney damage by suppressing inflammation, oxidative stress, and tubular apoptosis in cisplatin-induced AKI. Therefore, exogenous ß-HB as a pre-treatment emerges as a promising and novel strategy for preventing cisplatin-induced AKI.

ß-hydroxybutyrate ameliorates sepsis-induced acute kidney injury.

BACKGROUND: Sepsis is a major cause of acute kidney injury (AKI). Recent studies have demonstrated that ß-hydroxybutyrate (ß-HB) alleviates renal ischemia-reperfusion injury and cisplatin-induced renal injury in murine models. This study aimed to investigate whether ß-HB ameliorates sepsis-induced AKI (SIAKI) in a lipopolysaccharide (LPS)-induced mouse sepsis model. METHODS AND RESULTS: SIAKI was induced by intraperitoneally injecting LPS to C57BL/6 male mice. ß-HB was administrated intraperitoneally before LPS injection. The mice were divided into sham, ß-HB, LPS, and ß-HB + LPS groups. The histological damage score and serum creatinine level were significantly increased in the LPS group mice, but attenuated in the ß-HB + LPS group mice. The expression of phosphorylated nuclear factor-κB tumor necrosis factor-α/interleukin-6 and the number of F4/80-positive macrophages in the ß-HB + LPS group mice were lower than those in the LPS group mice. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells, cleaved caspase-3 expression, and Bax/Bcl-2 ratio in the ß-HB + LPS group mice were lower than those in the LPS group mice. CONCLUSION: ß-HB pre-treatment ameliorates SIAKI by reducing tubular apoptosis and inflammatory responses. Thus, ß-HB pre-treatment could be a potential prophylactic strategy against SIAKI.

Akt1 is involved in renal fibrosis and tubular apoptosis in a murine model of acute kidney injury-to-chronic kidney disease transition.

Maladaptive repair after acute kidney injury (AKI) can predispose patients to chronic kidney disease (CKD). However, the molecular mechanism underlying the AKI-to-CKD transition remains unclear. The Akt signaling pathway has been reported to be involved in the pathological processes of both AKI and CKD. In this study, we investigated the role of Akt1 in a murine model of the AKI-to-CKD transition. Wild-type (WT) and Akt1-/- mice were subjected to unilateral ischemia-reperfusion injury (UIRI), with their kidneys harvested after two days and two, four, and six weeks after UIRI. The dynamic changes in tubulointerstitial fibrosis, markers of tubular epithelial-mesenchymal transition (EMT), and tubular apoptosis were investigated. Akt1 of the three Akt isoforms was activated during the AKI-to-CKD transition. After UIRI, tubulointerstitial fibrosis and tubular EMT were significantly increased in WT mice, but were attenuated in Akt1-/- mice. The expression of the transforming growth factor (TGF)-ß1/Smad was increased in both WT and Akt1-/- mice, but was not different between the two groups. The levels of phosphorylated glycogen synthase kinase (GSK)-3ß, Snail, and ß-catenin in the Akt1-/- mice were lower than those in the WT mice. The number of apoptotic tubular cells and the expression of cleaved caspase-3/Bax were both lower in Akt1-/- mice than in WT mice. Genetic deletion of Akt1 was associated with attenuation of tubulointerstitial fibrosis, tubular EMT, and tubular apoptosis during the AKI-to-CKD transition. These findings were associated with TGF-ß1/Akt1/GSK-3ß/(Snail and ß-catenin) signaling independent of TGF-ß1/Smad signaling. Thus, Akt1 signaling could serve as a potential therapeutic target for inhibiting the AKI-to-CKD transition.

Effect of fluid overload on survival in patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

The association between fluid overload and survival has not been well elucidated in critically ill patients with sepsis-induced acute kidney injury (SIAKI) receiving continuous renal replacement therapy (CRRT). We investigated the optimal cutoff value of fluid overload for predicting mortality and whether minimizing fluid overload through CRRT is associated with a survival benefit in these patients. We examined 543 patients with SIAKI who received CRRT in our intensive care unit. The degree of cumulative fluid overload in relation to body weight was expressed as the percentage fluid overload (%FO). %FO was further subdivided into %FO from AKI diagnosis to CRRT initiation (%FOpreCRRT) and total fluid overload (%FOtotal). The best cutoff value of fluid overload for predicting the 28-day mortality was %FOpreCRRT > 4.6% and %FOtotal > 9.6%. Multivariable analysis demonstrated that patients with %FOpreCRRT > 4.6% and %FOtotal > 9.6% were 1.9 times and 3.37 times more likely to die than those with %FOpreCRRT ≤ 4.6% and %FOtotal ≤ 9.6%. The 28-day mortality was the highest in patients with %FOpreCRRT > 4.6% and %FOtotal > 9.6% (84.7%), followed by those with %FOpreCRRT ≤ 4.6% and %FOtotal > 9.6% (65.0%), %FOpreCRRT > 4.6% and %FOtotal ≤ 9.6% (43.6%), and %FOpreCRRT ≤ 4.6% and %FOtotal ≤ 9.6% (22%). This study demonstrated that fluid overload was independently associated with the 28-day mortality in critically ill patients with SIAKI. Future prospective studies are needed to determine whether minimizing fluid overload using CRRT improves the survival of these patients.

Procalcitonin decrease predicts survival and recovery from dialysis at 28 days in patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

Procalcitonin (PCT) is a biomarker for diagnosing infections and guiding antibiotic therapy. In this study, we investigated whether PCT can predict survival and recovery at 28 days in critically ill patients with sepsis-induced acute kidney injury (SIAKI) receiving continuous renal replacement therapy (CRRT). We examined 649 patients with SIAKI who underwent CRRT in our intensive care unit. In a multivariable Cox regression analysis, a single PCT level at CRRT initiation was not associated with survival in all patients. However, the higher % PCT decrease over 72 hours after CRRT initiation was independently associated with the higher chance of 28-day survival (per 10% decrease, hazard ratio [HR] for mortality: 0.87, 95% confidence interval [CI]: 0.85-0.89; P < 0.001). Among the survivors, the % PCT decrease over 72 hours after CRRT initiation, not a single PCT level at CRRT initiation, was independently associated with recovery from dialysis (per 10% decrease, HR for renal recovery: 1.28, 95% CI:1.21-1.36; P < 0.001). This study demonstrated that the higher % PCT decrease was independently associated with the higher chance of survival and recovery from dialysis at 28 days in critically ill patients with SIAKI receiving CRRT. Thus, a decrease in the PCT level, not a single PCT level at CRRT initiation, could be a valuable tool for predicting prognosis in these patients.

Graft-Versus-Host Disease Developed After En Bloc Kidney Transplant From a Pediatric Donor: A Case Report.

Graft-versus-host disease is a rare but a potentially fatal complication that can occur after kidney transplant. Furthermore, graft-versus-host disease after kidney transplant has been reported in only a few studies. We present a rare case of graft-versus-host disease in a patient who underwent kidney transplant. A patient who underwent hemodialysis received an en bloc kidney transplantfrom a pediatric donor, and the graft function was excellent. Mild diarrhea started on postoperative day 25. Six days after the onset of diarrhea, pancytopenia worsened and fever persisted. However, there were no test findings indicating infection or adverse medical effects. Graft-versus-host disease was diagnosed after a short tandem repeat evaluation of lymphocytes from the recipient's peripheral blood, which revealed 4.7% donor cells.The findings in this study provide insight into cases where symptoms such as fever and pancytopenia of unknown cause appear after kidney transplant, and we suggest that it is necessary to differentiate these symptoms from graft-versus-host disease.

Analysis of Risk Factors for Delayed Graft Function After Kidney Transplantation.

BACKGROUND: Delayed graft function (DGF) is a serious complication associated with worsening outcomes in kidney transplantation. To facilitate DGF risk reduction, this study aimed to identify the incidence and modifiable risk factors of this condition in kidney transplant patients. METHODS: This retrospective chart review included 220 patients who underwent kidney transplants between 2012 and 2021 at our kidney transplant center. Delayed graft function was defined as the requirement of hemodialysis within a week of transplantation. Clinical data from patients with DGF and those without this condition were compared to identify risk factors of DGF. RESULTS: Of 205 eligible patients, 20 (9.76%) developed DGF. In the univariate analysis, high hemoglobin level, deceased-donor type, and longer warm and cold ischemic times were significantly associated with DGF (P < .05). In the variable selection in logistic regression analysis, high hemoglobin level, with a cutoff value of 11.35 g/dL, and deceased-donor transplants were associated with higher DGF incidence (P < .05 for both factors). CONCLUSIONS: Our findings newly demonstrated that DGF occurred more frequently in patients with hemoglobin level >11.35 g/dL. As such, improvement in kidney transplantation outcomes could be achieved by reducing this modifiable risk factor.

Maintenance of the critical care system during the pandemic in non-COVID-19 patients requiring continuous renal replacement therapy: a single center experience.

BACKGROUND: During the COVID-19 pandemic, maintenance of essential healthcare systems became very challenging. We describe the triage system of our institute, and assess the quality of care provided to critically ill non-COVID-19 patients requiring continuous renal replacement therapy (CRRT) during the pandemic. METHODS: We introduced an emergency triage pathway early in the pandemic. We retrospectively reviewed the medical records of patients who received CRRT in our hospital from January 2016 to March 2021. We excluded end-stage kidney disease patients on maintenance dialysis. Patients were stratified as medical and surgical patients. The time from hospital arrival to intensive care unit (ICU) admission, the time from hospital arrival to intervention/operation, and the in-hospital mortality rate were compared before (January 2016 to December 2019) and during (January 2021 to March 2021) the pandemic. RESULTS: The mean number of critically ill patients who received CRRT annually in the surgical department significantly decreased during the pandemic in (2016-2019: 76.5 ± 3.1; 2020: 56; p < 0.010). Age, sex, and the severity of disease at admission did not change, whereas the proportions of medical patients with diabetes (before: 44.4%; after: 56.5; p < 0.005) and cancer (before: 19.4%; after: 32.3%; p < 0.001) increased during the pandemic. The time from hospital arrival to ICU admission and the time from hospital arrival to intervention/operation did not change. During the pandemic, 59.6% of surgical patients received interventions/operations within 6 hours of hospital arrival. In Cox's proportional hazard modeling, the hazard ratio associated with the pandemic was 1.002 (0.778-1.292) for medical patients and 1.178 (0.783-1.772) for surgical patients. CONCLUSION: Our triage system maintained the care required by critically ill non-COVID-19 patients undergoing CRRT at our institution.

Worsening or improving hypoalbuminemia during continuous renal replacement therapy is predictive of patient outcome: a single-center retrospective study.

BACKGROUND: Hypoalbuminemia at the initiation of continuous renal replacement therapy (CRRT) is a risk factor for poor patient outcomes. However, it is unknown whether the patterns of changes in serum albumin levels during CRRT can be used to predict patient outcomes. METHODS: This retrospective study analyzed data that had been consecutively collected from January 2016 to December 2020 at the Third Affiliated Hospital. We included patients with acute kidney injury who received CRRT for ≥ 72 h. We divided the patients into four groups based on their serum albumin levels (albumin ≥ 3.0 g/dL or < 3.0 g/dL) at the initiation and termination of CRRT. RESULTS: The 793 patients in this study were categorized into the following albumin groups: persistently low, 299 patients (37.7%); increasing, 85 patients (10.4%); decreasing, 195 patients (24.6%); and persistently high, 214 patients (27.1%). In-hospital mortality rates were highest in the persistently low and decreasing groups, followed by the increasing and persistently high groups. The hazard ratio for in-hospital mortality was 0.481 (0.340-0.680) in the increasing group compared to the persistently low group; it was 1.911 (1.394-2.620) in the decreasing group compared to the persistently high group. The length of ICU stay was 3.55 days longer in the persistently low group than in the persistently high group. CONCLUSIONS: Serum albumin levels changed during CRRT, and monitoring of patterns of change in serum albumin levels is useful for predicting in-hospital mortality and the length of ICU stay.

1,25-dihydroxyvitamin D deficiency is independently associated with cardiac valve calcification in patients with chronic kidney disease.

Cardiac valve calcification is highly prevalent in patients with chronic kidney disease (CKD). Low vitamin D levels are associated with vascular calcification in CKD. However, the association between vitamin D levels and cardiac valve calcification is unknown. A total of 513 patients with pre-dialysis CKD were included in this cross-sectional study. Aortic valve calcification (AVC) and mitral valve calcification (MVC) were assessed using two-dimensional echocardiography. The associations between AVC and MVC and baseline variables were investigated using logistic regression analyses. In multivariable analysis, serum 1,25(OH)2D level was independently associated with AVC (odds ratio [OR], 0.87; P < 0.001) and MVC (OR, 0.92; P < 0.001). Additionally, age, diabetes, coronary heart disease, calcium × phosphate product, and intact parathyroid hormone levels were independently associated with AVC and MVC. Systolic blood pressure was independently associated with AVC. A receiver-operating characteristic (ROC) curve analysis showed that the best cutoff values of serum 1,25(OH)2D levels for predicting AVC and MVC were ≤ 12.5 and ≤ 11.9 pg/dl, respectively. Serum 1,25(OH)2D deficiency is independently associated with AVC and MVC in patients with CKD, suggesting that serum 1,25(OH)2D level may be a potential biomarker of AVC and MVC in these patients.

Immunoglobulin A nephropathy in a patient with neurofibromatosis type 1: A case report and literature review.

RATIONALE: Neurofibromatosis type 1 (NF-1) is an autosomal-dominant neurocutaneous disorder that affects the skin, bones, and nervous system. The most common manifestation of kidney involvement is renal artery stenosis; glomerulonephritis is extremely rare. In this case report, we present a patient with NF-1 and immunoglobulin A nephropathy (IgAN). PATIENT CONCERNS: A 51-year-old Korean man previously diagnosed with NF-1 presented with persistent proteinuria and hematuria identified during a routine medical check-up. He had no history of hypertension or diabetes, and denied a history of alcohol use or smoking. DIAGNOSIS: The contrast-enhanced computed tomography scan revealed normal-sized kidneys and no evidence of renal artery stenosis. On the day of the kidney biopsy, laboratory tests showed a serum creatinine level of 1.1 mg/dL, urine protein/creatinine ratio of 1.3 g/g, and urine red blood cell count of >10 to 15/HPF. The kidney biopsy sample revealed IgAN grade III, according to Lee glomerular grading system. INTERVENTION: The patient was advised to take 4 mg of perindopril. OUTCOME: Three months after the treatment, the urine protein/creatinine ratio decreased to 0.6 g/g, with no change in the serum creatinine level (1.03 mg/dL). LESSONS: A genetic link between NF-1 and IgAN or other glomerular diseases is not established. However, activation of the mTOR pathway may explain this association.

Clinical outcomes and prognostic factors of mortality in liver cirrhosis patients on continuous renal replacement therapy in two tertiary hospitals in Korea.

BACKGROUND: Data on liver cirrhosis (LC) patients undergoing continuous renal replacement therapy (CRRT) are lacking despite of the dismal prognosis. We therefore evaluated clinical characteristics and predictive factors related to mortality in LC patients undergoing CRRT. METHODS: We performed a retrospective observational study at two tertiary hospitals in Korea. A total of 229 LC patients who underwent CRRT were analyzed. Patients were classified into survivor and non-survivor groups. We used multivariable Cox regression analyses to identify predictive factors of in-hospital mortality. RESULTS: During a median follow-up of 5 days (interquartile range, 1-19 days), in-hospital mortality rate was 66.4%. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.06; p = 0.02), Model for End-Stage Liver Disease (MELD) score (HR, 1.08; 95% CI, 1.04-1.11; p <0.001), and delivered CRRT dose (HR, 0.95; 95% CI, 0.92-0.98; p = 0.002) were significant risk factors for in-hospital mortality. Patients with a CRRT delivered dose < 25 mL/kg/hr had a higher mortality rate than those with a delivered dose > 35 mL/kg/hr (HR, 3.13; 95% CI, 1.62-6.05; p = 0.001). Subgroup analysis revealed that a CRRT delivered dose < 25 mL/kg/hr was a significant risk factor for in-hospital mortality among LC patients with a MELD score ≥ 30. CONCLUSION: High APACHE II score, high MELD score, and low delivered CRRT dose were significant risk factors for in-hospital mortality. CRRT delivered dose impacted mortality significantly, especially in patients with a MELD score ≥ 30.

Association between serum uric acid and left ventricular hypertrophy/left ventricular diastolic dysfunction in patients with chronic kidney disease.

BACKGROUND: The level of serum uric acid (SUA) has been reported to be associated with left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). However, this association remains unclear in patients with chronic kidney disease (CKD). METHODS: A total of 1025 patients with pre-dialysis CKD with preserved left ventricular systolic function were enrolled in this cross-sectional study. The LVH and LVDD were assessed using two-dimensional echocardiography and tissue Doppler imaging. The associations of LVH/LVDD with clinical and laboratory variables were investigated using univariable and multivariable logistic regression analyses. RESULTS: In a multivariable analysis, the SUA level was an independent predictor of LVH (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 1.31-1.50, P < 0.001). In addition, patient age, systolic blood pressure, intact parathyroid hormone levels, and left atrial volume index levels were independent predictors of LVH. The SUA level was also an independent predictor of LVDD (OR: 1.93, 95% CI: 1.53-2.43, P < 0.001). Furthermore, systolic blood pressure and left atrial volume index levels were an independent predictor of LVDD. Receiver-operating characteristic curve analysis showed that the best cutoff values of SUA levels for identifying LVH and LVDD were ≥ 7.5 mg/dL and ≥ 6.3 mg/dL, respectively. CONCLUSION: The SUA level was an independent predictor of LVD and LVDD in patients with CKD, suggesting that SUA could be a biomarker for LVH and LVDD.

Median nerve swelling is an independent risk factor of carpal tunnel syndrome in chronic hemodialysis patients.

Carpal tunnel syndrome (CTS) has a wide variety of underlying causes and occurs in association with dialysis. Early diagnosis is essential to prevent permanent nerve damage and functional sequelae. We evaluated the association between CTS and cross-sectional area (CSA) of the median nerve in chronic hemodialysis (HD) patients. Patients with end-stage renal disease on maintenance HD via arteriovenous fistula were enrolled. We divided 43 patients into two groups; patients diagnosed with CTS (n = 19) and patients without CTS (n = 24). The median nerve CSA was measured at the wrist (CSA-W) and forearm (CSA-F) by ultrasonography. Median nerve swelling was assessed by the wrist-to-forearm ratio (WFR). There were no significant differences in the underlying causes of chronic kidney disease and adequacy of dialysis between the two groups (p = NS). The patients with CTS showed significantly higher WFR than the patients without CTS (p = 0.001). Univariate Cox regression analysis revealed that WFR >1.25 (odds ratio, 6.30; 95% confidence interval, 1.44-27.45; p = 0.014) was associated with CTS in HD patients. The factors traditionally associated with CTS such as age, sex, diabetes, vintage of HD, ß2-MG, intact PTH, and Kt/V were not associated with CTS. After adjustment for age and sex, we found a strong correlation between CTS and the WFR >1.25 (odds ratio, 10.8; 95% confidence interval, 1.85-62.4; p = 0.008). High WFR was associated with the development of CTS, and median nerve swelling was an independent risk factor of CTS in chronic HD patients.

Role of Akt1 in renal fibrosis and tubular dedifferentiation during the progression of acute kidney injury to chronic kidney disease.

BACKGROUND/AIMS: Acute kidney injury (AKI) is an underestimated yet important risk factor for the development of chronic kidney disease (CKD), characterized by tubulointerstitial fibrosis and tubular dedifferentiation. Tubular dedifferentiation, which is associated with the loss of epithelial markers and the gain of mesenchymal features, is thought to be involved in tubulointerstitial fibrosis. As protein kinase B/Akt is involved in the development of CKD, we investigated the role of Akt1, one of the three Akt isoforms, in a murine model of AKI-to-CKD progression. METHODS: We subjected C57BL/6 male mice to unilateral ischemia-reperfusion injury (UIRI) and harvested their kidneys after 6 weeks. Mice were divided into four groups, namely, wild-type (WT) UIRI, Akt1-/- UIRI, WT sham, and Akt1-/- sham. RESULTS: Akt1 (but not Akt2 or Akt3) was markedly activated in WT UIRI mice than in WT sham mice. Tubulointerstitial fibrosis and tubular dedifferentiation significantly increased in WT UIRI mice, but were attenuated in Akt1-/- UIRI mice. Both WT UIRI and Akt1-/- UIRI mice showed markedly upregulated transforming growth factor-ß1 (TGF-ß1)/Smad signaling compared with WT sham mice. However, TGF-ß1/Smad expression did not differ between the two groups. The levels of phosphorylated GSK-3ß, ß-catenin, and Snail were attenuated in Akt1-/- UIRI mice compared with those in WT UIRI mice. CONCLUSION: Deletion of Akt1 results in the attenuation of renal fibrosis and tubular dedifferentiation, independent of TGF-ß1/Smad signaling, during AKI-to-CKD progression in a UIRI without contralateral nephrectomy model. Thus, Akt1 may serve as a therapeutic target in AKI-to-CKD progression.

STOX1 deficiency is associated with renin-mediated gestational hypertension and placental defects.

The pathogenesis of preeclampsia and other hypertensive disorders of pregnancy remains poorly defined despite the substantial burden of maternal and neonatal morbidity associated with these conditions. In particular, the role of genetic variants as determinants of disease susceptibility is understudied. Storkhead-box protein 1 (STOX1) was first identified as a preeclampsia risk gene through family-based genetic linkage studies in which loss-of-function variants were proposed to underlie increased preeclampsia susceptibility. We generated a genetic Stox1 loss-of-function mouse model (Stox1 KO) to evaluate whether STOX1 regulates blood pressure in pregnancy. Pregnant Stox1-KO mice developed gestational hypertension evidenced by a significant increase in blood pressure compared with WT by E17.5. While severe renal, placental, or fetal growth abnormalities were not observed, the Stox1-KO phenotype was associated with placental vascular and extracellular matrix abnormalities. Mechanistically, we found that gestational hypertension in Stox1-KO mice resulted from activation of the uteroplacental renin-angiotensin system. This mechanism was supported by showing that treatment of pregnant Stox1-KO mice with an angiotensin II receptor blocker rescued the phenotype. Our study demonstrates the utility of genetic mouse models for uncovering links between genetic variants and effector pathways implicated in the pathogenesis of hypertensive disorders of pregnancy.