Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organs, including the brain, skin, lung, and kidney. Among the multiple comorbidities in TSC, bone mineral disturbances remain relatively unrecognized, and only a few studies have reported alteration in calcium homeostasis. Hypocalcemia is a serious medical condition in patients with TSC who are at high risk for seizures. Therefore, hypocalcemia should be thoroughly evaluated by obtaining a history of associated medication use and measuring vitamin D levels. Here, we report the case of a patient with TSC who presented with severe hypocalcemia which may have been related to a history of anticonvulsant use and a recent decline in kidney function, and was successfully treated with calcium and vitamin D replacement.

Background/Aims: This study aimed to investigate long-term temporal trends and outcomes of biopsy-proven kidney diseases in a multicenter kidney biopsy cohort, focusing on hypertension and diabetes, the leading causes of end-stage kidney disease (ESKD). Methods: The study included a total of 21,426 patients who underwent kidney biopsy from 1979 to 2018 in 18 hospitals in Korea. We selected subgroups of adults with diabetes (n = 2,813) or clinically presumed hypertensive nephrosclerosis (HTN, n = 2,917). Clinical, demographic, and laboratory data were collected in conjunction with pathologic findings. The prevalence of pathologically confirmed kidney diseases over time and their associations with clinical outcomes were evaluated. Results: The prevalence of biopsy-proven diabetic nephropathy (DN) has increased significantly from 2.5% to 6.0% in the total cohort in the recent 30 yearswith an increase in the prevalence of diabetes. Approximately 68% of total diabeticpatients had non-diabetic renal disease (NDRD); the proportion was retained since 2000s. DN showed a significantly higher risk of ESKD than NDRD (hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.35 to 1.88). The prevalence of biopsy- proven HT-N remained < 2% in the total cohort for several decades. There was no difference in risks of ESKD between patients with or without biopsy-proven HT-N (HR, 0.93; 95% CI, 0.54 to 1.59). Conclusions In recent decades, the prevalence of diabetes and DN has significantlyincreased in the kidney biopsy cohort, showing an increased risk of ESKD. Despite the large numbers of patients meeting the clinical criteria of HT-N, most of those were diagnosed with pathologic diagnoses other than HT-N.

Background: s: Recently, alternative surrogate endpoints such as a 30% or 40% decline in estimated glomerular filtration rate (eGFR) or eGFR slope over 2 to 3 years have been proposed for predicting renal outcomes. However, the impact of GFR estimation methods on the accuracy and effectiveness of surrogate markers is unknown. Methods: We retrospectively enrolled participants in health screening programs at three hospitals from 1995 to 2009. We defined two different participant groups as YR1 and YR3, which had available 1-year or 3-year eGFR values along with their baseline eGFR levels. We compared the effectiveness of eGFR percentage change or slope to estimate end-stage renal disease (ESRD) risk according to two estimating equations (modified Modification of Diet in Renal Disease equation [eGFRm] and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation [eGFRc]) for GFR. Results: In the YR1 and YR3 groups, 9,971 and 10,171 candidates were enrolled and ESRD incidence during follow-up was 0.26% and 0.19%, respectively. The eGFR percentage change was more effective than eGFR slope in estimating ESRD risk, regardless of the method of estimation. A 40% of decline in eGFR was better than 30%, and a 3-year baseline period was better than a 1-year period for prediction accuracy. Although some diagnostic indices from the CKD-EPI equation were better, we found no significant differences in the discriminative ability and hazard ratios for incident ESRD between eGFRc and eGFRm in either eGFR percentage change or eGFR slope. Conclusion There were no significant differences in the prediction accuracy of GFR percentage change or eGFR slope between eGFRc and eGFRm in the general population.

Background: s: Recently, alternative surrogate endpoints such as a 30% or 40% decline in estimated glomerular filtration rate (eGFR) or eGFR slope over 2 to 3 years have been proposed for predicting renal outcomes. However, the impact of GFR estimation methods on the accuracy and effectiveness of surrogate markers is unknown. Methods: We retrospectively enrolled participants in health screening programs at three hospitals from 1995 to 2009. We defined two different participant groups as YR1 and YR3, which had available 1-year or 3-year eGFR values along with their baseline eGFR levels. We compared the effectiveness of eGFR percentage change or slope to estimate end-stage renal disease (ESRD) risk according to two estimating equations (modified Modification of Diet in Renal Disease equation [eGFRm] and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation [eGFRc]) for GFR. Results: In the YR1 and YR3 groups, 9,971 and 10,171 candidates were enrolled and ESRD incidence during follow-up was 0.26% and 0.19%, respectively. The eGFR percentage change was more effective than eGFR slope in estimating ESRD risk, regardless of the method of estimation. A 40% of decline in eGFR was better than 30%, and a 3-year baseline period was better than a 1-year period for prediction accuracy. Although some diagnostic indices from the CKD-EPI equation were better, we found no significant differences in the discriminative ability and hazard ratios for incident ESRD between eGFRc and eGFRm in either eGFR percentage change or eGFR slope. Conclusion There were no significant differences in the prediction accuracy of GFR percentage change or eGFR slope between eGFRc and eGFRm in the general population.

Background: The significance of ambulatory blood pressure (ABP) in Korean patients with chronic kidney disease (CKD) in relation to renal outcome or death remains unclear. We investigated the role of ABP in predicting end-stage renal disease or death in patients with CKD. Methods: We enrolled 387 patients with hypertension and CKD who underwent ABP monitoring and were followed for 1 year. Data on clinical parameters and outcomes from August 2014 to May 2018 were retrospectively collected. The composite endpoint was end-stage renal disease or death. Patients were grouped according to the mean ABP. Results: There were 66 endpoint events, 52 end-stage renal disease cases, and 15 mortalities. Among all patients, one developed end-stage renal disease and died. Mean ABP in the systolic and diastolic phases were risk factors for the development of composite outcome with hazard ratios of 1.03 (95% confidence interval [CI], 1.01-1.04; P < 0.001) and 1.04 (95% CI, 1.02-1.07; P = 0.001) for every 1 mmHg increase in BP, respectively. Patients with mean ABP between 125/75 and 130/80 mmHg had a 2.56-fold higher risk for the development of composite outcome (95% CI, 0.72-9.12; P = 0.147) as compared to those with mean ABP ≤ 125/75 mmHg. Patients with mean ABP ≥ 130/80 mmHg had a 4.79-fold higher risk (95% CI, 1.68-13.70; P = 0.003) compared to those with mean ABP ≤ 125/75 mmHg. Office blood pressure (OBP) was not a risk factor for the composite outcome when adjusted for covariates. Conclusion In contrast to OBP, ABP was a significant risk factor for end-stage renal disease or death in CKD patients.

Background: Serum uric acid (SUA) is recognized as a risk factor for chronic kidney disease (CKD) and mortality. However, there is controversy as to whether a high or low level of SUA is related to the risk of CKD progression or death, and whether it differs between males and females. Methods: We included 143,762 adults who underwent voluntary health screening between 1995 and 2009 in Korea. For each sex, we divided participants into sex-specific quintiles according to SUA levels and compared end-stage renal disease (ESRD) incidence and mortality between the groups with low and high SUA levels and those with middle SUA levels. Sex-specific Cox proportional hazard analyses were performed for ESRD and all-cause mortality. Results: Among the 143,762 participants, 0.2% (n = 272) developed ESRD. The hazard ratio (HR) of ESRD was higher in the highest (adjusted HR, 2.13; 95% confidence interval [CI], 1.18–3.84) and lowest (adjusted HR, 1.90; 95% CI, 1.02–3.51) SUA quintiles than in the middle SUA quintile in males and the highest SUA quintile in females (adjusted HR, 2.31; 95% CI, 1.10–4.84). Four-point three percent (n = 6,215) of participants died during a mean follow-up period of 157 months. The hazard ratio (HR) of all-cause mortality was higher in the highest SUA quintile than in the middle SUA quintile in males (adjusted HR, 1.15; 95% CI, 1.03–1.28) and females (adjusted HR, 1.17; 95% CI, 1.01–1.35). Conclusion Elevated levels of SUA are associated with increased risk for ESRD and all-cause mortality in both sexes. Low levels of SUA might be related to ESRD and death only in males, showing U-shaped associations. Our findings suggest sex-specific associations between SUA levels and ESRD development and mortality.

This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. Methods: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. Results: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21–1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78–2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09–1.99; p = 0.01) but not among those with low disease severity. Conclusion: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

BACKGROUND: The plasma levels of cell-free DNA (cfDNA) are known to be elevated under inflammatory or apoptotic conditions. Increased cfDNA levels have been reported in hemodialysis (HD) patients. The aim of this study was to investigate the clinical significance of cfDNA in HD patients. METHODS: A total of 95 patients on HD were enrolled. We measured their predialysis cfDNA levels using real-time EIF2C1 gene sequence amplification and analyzed its association with certain clinical parameters. RESULTS: The mean plasma cfDNA level in the HD patients was 3,884 +/- 407 GE/mL, and the mean plasma cfDNA level in the control group was 1,420 +/- 121 GE/mL (P < 0.05). Diabetic patients showed higher plasma cfDNA levels compared with nondiabetic patients (P < 0.01). Patients with cardiovascular complications also showed higher plasma cfDNA levels compared with those without cardiovascular complication (P < 0.05). In univariable analysis, the cfDNA level was associated with 3-month mean systolic blood pressure (SBP), white blood cell, serum albumin, creatinine (Cr), normalized protein catabolic rate in HD patients. In diabetic patients, it was significantly correlated with SBP, hemoglobin A1c, and serum albumin. In multivariate analysis, SBP was the independent determinant for the cfDNA level. In diabetic patients, cfDNA level was independently associated with hemoglobin A1c and SBP. CONCLUSIONS: In patients with HD, cfDNA is elevated in diabetic patients and patients with cardiovascular diseases. Uncontrolled hypertension and poor glycemic control are independent determinants for the elevated cfDNA. Our data suggest that cfDNA might be a marker of vascular injury rather than proinflammatory condition in HD patients.
Blood Pressure* ; Cardiovascular Diseases ; Creatinine ; Diabetes Mellitus ; DNA* ; Humans ; Hypertension ; Leukocytes ; Multivariate Analysis ; Plasma* ; Renal Dialysis* ; Serum Albumin ; Vascular System Injuries

Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. Methods: This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays. Results: When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00–0.02) and 0.02 (95% CI, 0.01–0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. Conclusion: Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

A high degree of sensitization to human leukocyte antigen requires more intensive induction therapy; however, this increases vulnerability to opportunistic infections following kidney transplantation. Although recent studies have suggested that combined induction therapy with antithymocyte globulin and rituximab would be more effective in highly sensitized kidney recipients, we experienced a case of near-fatal invasive pulmonary aspergillosis 2 months after combined induction and early rejection therapy for graft dysfunction. Fortunately, the patient recovered with intensive antifungal treatment and lung lobectomy for a necrotic cavity. Antifungal prophylaxis should be considered in cases undergoing intensive induction therapy.
Antilymphocyte Serum* ; Humans ; Immunoglobulins* ; Invasive Pulmonary Aspergillosis* ; Kidney Transplantation* ; Kidney* ; Leukocytes ; Lung ; Opportunistic Infections ; Plasmapheresis* ; Rituximab* ; Transplants