Optimal Timing of Serum Creatinine Measurement for KDPI Scoring to Predict Postoperative Renal Function in Deceased Donor Kidney Transplantation.

INTRODUCTION: The widely employed Kidney Donor Profile Index (KDPI) scoring system, designed for assessing deceased donors (DD), plays a pivotal role in predicting graft function post kidney transplantation (KT). Given the dynamic nature of renal function, including serum creatinine (sCr), in managing DDs, it remains uncertain optimal timing to use KDPI for assessing postoperative graft function. METHODS: In this retrospective review, we assessed 246 DDs who were managed within a donor management program from January 2010 to December 2021. We collected sCr values for KDPI scoring at admission, peak, and last measurements before KT. Recipient data included occurrence of slow graft function (SGF), delayed graft function (DGF), and glomerular filtration rate (GFR) at one-year post-transplantation (1 Y). Using Receiver Operating Characteristic (ROC) and Pearson correlation analyses, we explored correlations of KDPI score (admission, peak, last) with graft function (SGF, DGF, GFR 1 Y). RESULTS: The average age of DDs and recipients was 49.78 ± 13.37 and 52.54 ± 10.49 years, respectively, with mean KDPI values at admission, peak, and last measurements of 62.36 ± 25.44, 66.94 ± 24.73, and 63.75 ± 25.80. After transplantation, SGF was observed in 81 recipients (32.9%) and DGF in 32 (13.0%). For SGF, the Area Under the Curve (AUC) from ROC analysis were 0.684 (95% CI, 0.615-0.753; P < .001) at admission, 0.691 (0.623-0.759; P < .001) at peak, and 0.697 (0.630-0.765; P < .001) at the last measurement. In predicting DGF, the corresponding AUC values were 0.746 (0.661-0.831; P < .001) at admission, 0.724 (0.637-0.810; P < .001) at peak, and 0.721 (0.643-0.809; P < .001) at the last. Moreover, KDPI scores at all time points-admission, peak, and last-moderately correlated with GFR 1 Y (R = -0.426, -0.423, -0.417). CONCLUSION: KDPI measurements at all time points, particularly admission, would be more effective in predicting DGF in DDKT.

Blood pressure control in diabetic kidney disease: a post-hoc analysis of the FANTASTIC trial.

BACKGROUND: The target blood pressure (BP) value is unclear for diabetic kidney disease (DKD). Therefore, we aimed to evaluate the effect of strict BP control or 'on treatment' BP on clinical outcomes in patients with DKD. METHODS: A post-hoc analysis of the prespecified secondary outcomes of the FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial, a randomized multicenter double-blind phase III trial. Eligible patients were aged ≥ 19 years with DKD. We assigned 341 participants with DKD to BP control strategy (standard-systolic BP [SBP] < 140 mmHg versus strict-SBP < 130 mmHg). The outcome was the occurrence of cardiovascular events and renal events. Separate analyses were performed to compared the risk of outcome according to achieved average BP levels. RESULTS: A total of 341 participants were included in the analysis. Over a median follow-up of 2.8 years, cardiovascular/renal events were observed in 25 (7.3%) participants. Mean (SD) SBPs in the standard and strict BP control group were 140.2 (11.6) and 140.2 (11.9) mmHg, respectively. The strict BP control group did not show significantly reduced risk of cardiovascular/renal events (HR 1.32; 95% CI 0.60-2.92]). In the post-hoc analyses using achieved BP, achieved average SBP of 130-139 mmHg resulted in reduced risk of cardiovascular/renal events (HR 0.15; 95% CI 0.03-0.67) compared to achieved average SBP ≥ 140 mmHg, whereas further reduction in achieved average SBP < 130 mmHg did not impart additional benefits. CONCLUSION: In patients with DKD, targeting a SBP of less than 130 mmHg, as compared with less than 140 mmHg, did not reduce the rate of a composite of cardiovascular and renal events. Achieved SBP of 130-139 mmHg was associated with a decreased risk for the primary outcome in patients with DKD. TRIAL REGISTRATION: ClinicalTirals.gov Identifier: NCT02620306, registered December 3, 2015. ( https://clinicaltrials.gov/study/NCT02620306 ).

Kidney Health Plan 2033 in Korea: bridging the gap between the present and the future.

In response to the increase in the prevalence of chronic kidney disease (CKD) in Korea, the growth of patients requiring renal replacement therapy and the subsequent increase in medical costs, the rapid expansion of patients with end-stage kidney disease (ESKD), and the decrease in patients receiving home therapy, including peritoneal dialysis, the Korean Society of Nephrology has proclaimed the new policy, Kidney Health Plan 2033 (KHP 2033). KHP 2033 would serve as a milestone to bridge the current issues to a future solution by directing the prevention and progression of CKD and ESKD, particularly diabetic kidney disease, and increasing the proportion of home therapy, thereby reducing the socioeconomic burden of kidney disease and improving the quality of life. Here, we provide the background for the necessity of KHP 2033, as well as the contents of KHP 2033, and enlighten the Korean Society of Nephrology's future goals. Together with patients, healthcare providers, academic societies, and national policymakers, we need to move forward with goal-oriented drive and leadership to achieve these goals.

Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys.

Background: Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Changes in glucose metabolism among recipients with diabetes 1 year after kidney transplant: a multicenter 1-year prospective study.

Background: Diabetes mellitus is a common and crucial metabolic complication in kidney transplantation. It is necessary to analyze the course of glucose metabolism in patients who already have diabetes after receiving a transplant. In this study, we investigated the changes in glucose metabolism after transplantation, and a detailed analysis was performed on some patients whose glycemic status improved. Methods: The multicenter prospective cohort study was conducted between 1 April 2016 and 31 September 2018. Adult patients (aged 20 to 65 years) who received kidney allografts from living or deceased donors were included. Seventy-four subjects with pre-transplant diabetes were followed up for 1 year after kidney transplantation. Diabetes remission was defined as the results of the oral glucose tolerance test performed one year after transplantation and the presence or absence of diabetes medications. After 1-year post-transplant, 74 recipients were divided into the persistent diabetes group (n = 58) and the remission group (n = 16). Multivariable logistic regression was performed to identify clinical factors associated with diabetes remission. Results: Of 74 recipients, 16 (21.6%) showed diabetes remission after 1-year post-transplant. The homeostatic model assessment for insulin resistance numerically increased in both groups throughout the first year after transplantation and significantly increased in the persistent diabetes group. The insulinogenic index (IGI30) value significantly increased only in the remission group, and the IGI30 value remained low in the persistent diabetes group. In univariate analysis, younger age, newly diagnosed diabetes before transplantation, low baseline hemoglobin A1c, and high baseline IGI30 were significantly associated with remission of diabetes. After multivariate analysis, only newly diagnosed diabetes before transplantation and IGI30 at baseline were associated with remission of diabetes (34.00 [1.192-969.84], P = 0.039, and 17.625 [1.412-220.001], P = 0.026, respectively). Conclusion: In conclusion, some kidney recipients with pre-transplant diabetes have diabetes remission 1 year after transplantation. Our prospective study revealed that preserved insulin secretory function and newly diagnosed diabetes at the time of kidney transplantation were favorable factors for which glucose metabolism did not worsen or improve 1 year after kidney transplantation.

The eGFR Decline as a Risk Factor for Metabolic Syndrome in the Korean General Population: A Longitudinal Study of Individuals with Normal or Mildly Reduced Kidney Function.

Metabolic syndrome (MS) is a risk factor for the development and progression of chronic kidney disease (CKD). However, it is unclear whether decreased renal function affects MS. Through a longitudinal study, we investigated the effect of estimated glomerular filtration rate (eGFR) changes on MS in participants with an eGFR above 60 mL/min/1.73 m2. A cross-sectional (n = 7107) and a 14-year longitudinal study (n = 3869) were conducted to evaluate the association between MS and eGFR changes from the Korean Genome and Epidemiology Study data. The participants were categorized by their eGFR levels (60-75, 75-90, and 90-105 versus ≥ 105 mL/min/1.73 m2). In a cross-sectional analysis, the MS prevalence was significantly increased with a decline in the eGFR in a fully adjusted model. The odds ratio of individuals with an eGFR of 60-75 mL/min/1.73 m2 was observed to be the highest (2.894; 95% confidence interval (CI), 1.984-4.223). In the longitudinal analysis, incident MS significantly increased with an eGFR decline in all the models, with the highest hazard ratio in the lowest eGFR group (1.803; 95% CI, 1.286-2.526). In joint interaction analysis, all covariates showed a significant joint effect with an eGFR decline on the incident MS. MS incidents are associated with eGFR changes in the general population without CKD.

SH3YL1 Protein Predicts Renal Outcomes in Patients with Type 2 Diabetes.

NADPH oxidase (NOX)-derived oxidative stress is an important factor in renal progression, with NOX4 being the predominant NOX in the kidney. Recently, Src homology 3 (SH3) domain-containing YSC84-like 1 (SH3YL1) was reported to be a regulator of NOX4. In this study, we tested whether the SH3YL1 protein could predict 3-year renal outcomes in patients with type 2 diabetes. A total of 131 patients with type 2 diabetes were enrolled in this study. Renal events were defined as a 15% decline in the estimated glomerular filtration rate (eGFR) from the baseline, the initiation of renal replacement therapy, or death during the 3 years. The levels of the urinary SH3YL1-to-creatinine ratio (USCR) were significantly different among the five stages of chronic kidney disease (CKD) and the three groups, based on albuminuria levels. The USCR levels showed a significant negative correlation with eGFR and a positive correlation with the urinary albumin-to-creatinine ratio (UACR). Plasma SH3YL1 levels were significantly correlated with UACR. The highest tertile group of USCR and plasma SH3YL1 had a significantly lower probability of renal event-free survival. Furthermore, the highest tertile group of USCR showed a significant association with the incidence of renal events after full adjustment: adjusted hazard ratio (4.636: 95% confidence interval, 1.416-15.181, p = 0.011). This study suggests that SH3YL1 is a new diagnostic biomarker for renal outcomes in patients with type 2 diabetes.

APX­115A, a pan­NADPH oxidase inhibitor, reduces the degree and incidence rate of dry eye in the STZ­induced diabetic rat model.

Dye eye disease (DED) is a common ocular disorder in patients with diabetes. It has been reported that APX-115A, a pan-nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase inhibitor, has an apoptosis-inducing effect on Epstein-Barr virus-infected retinal epithelial cells, but its effects in DED are poorly understood. Therefore, a rat model of diabetes was used in the present study to investigate whether APX-115A has an impact on DED in diabetic rats. A diabetic model was established in male Sprague Dawley rats via the intraperitoneal injection of streptozotocin. The eyeballs of the rats were treated with a solution containing APX-115A or a saline control. Tear secretion was measured with the phenol red thread tear test, and the morphology of the eyeball and lacrimal gland tissues was determined using hematoxylin and eosin staining. In addition, localization of NAPDH oxidase 2 (NOX2) in the eyeball and lacrimal gland tissues was detected by immunohistochemistry. The APX-115A treatment had no effect on body weight, blood glucose level or the size of the lacrimal glands. However, morphological changes, namely intracellular vacuoles and acinar atrophy, were observed in the lacrimal glands of the diabetic rats, and APX-115A treatment attenuated these changes. Immunohistochemistry revealed that NOX2 expression was decreased in the lacrimal glands of the diabetic rats, and APX-115A treatment did not attenuate the reduction in NOX2. The corneas of the diabetic rats treated with APX-115A exhibited no change in thickness but had lower NOX2 expression levels compared with those of the control diabetic rats. APX-115A also increased tear secretion and ameliorated the histological changes associated with diabetes. Furthermore, the NOX2 expression levels in the corneas of the diabetic rats treated with APX-115A were restored to the levels observed in normal rats. These findings suggest that APX-115A has potential as a therapeutic agent for DED.

Association of a low protein diet with depressive symptoms and poor health-related quality of life in CKD.

OBJECTIVES: A low protein diet (LPD) for chronic kidney disease (CKD) is a core dietary therapy to slow CKD progression. A study showed depressive symptoms are more common in populations with an LPD. In this cross-sectional study, we evaluated depressive symptoms and health-related quality of life (HRQOL) in patients with CKD. METHODS: A total of 571 CKD patients were enrolled in this study. The LPD was defined with dietary protein intake ≤0.8 g/kg/day. We divided the CKD into mild CKD and advanced CKD according to severity, as well as diabetic kidney disease (DKD) and non-DKD according to DM. The logistic regression analysis was performed to evaluate the association between an LPD and depressive symptoms as well as HRQOL in CKD patients and each subgroup. RESULTS: An LPD had significantly higher unadjusted Odds Ratio (OR) (1.81, [95% for Confidence Interval (CI), 1.18-2.76]) and multivariate-adjusted OR (1.80, [1.15-2.81]) for depressive symptoms. Moreover, an LPD showed significantly higher unadjusted OR (2.08, 1.44-3.01]) and multivariate OR (2.04, [1.38-3.02]) for poor HRQOL. In DKD subgroups, an LPD had a significant increase in unadjusted OR (2.00, [1.12-3.57]) and multivariate OR (1.99, [1.01-3.44]) for depressive symptoms. The advanced CKD group also showed that an LPD had significantly higher unadjusted OR (1.97, [1.13-3.42]) and multivariate OR (2.03, [1.12-3.73]) for depressive symptoms. CONCLUSIONS: An LPD for CKD patients was significantly associated with depressive symptoms and poor HRQOL. Subgroup analysis indicated that DKD and advanced CKD are more predisposed to depressive symptoms and poor HRQOL.

The Role of V-Set Ig Domain-Containing 4 in Chronic Kidney Disease Models.

V-set Ig domain-containing 4 (VSIG4) regulates an inflammatory response and is involved in various diseases. However, the role of VSIG4 in kidney diseases is still unclear. Here, we investigated VSIG4 expression in unilateral ureteral obstruction (UUO), doxorubicin-induced kidney injury mouse, and doxorubicin-induced podocyte injury models. The levels of urinary VSIG4 protein significantly increased in the UUO mice compared with that in the control. The expression of VSIG4 mRNA and protein in the UUO mice was significantly upregulated compared with that in the control. In the doxorubicin-induced kidney injury model, the levels of urinary albumin and VSIG4 for 24 h were significantly higher than those in the control mice. Notably, a significant correlation was observed between urinary levels of VSIG4 and albumin (r = 0.912, p < 0.001). Intrarenal VSIG4 mRNA and protein expression were also significantly higher in the doxorubicin-induced mice than in the control. In cultured podocytes, VSIG4 mRNA and protein expressions were significantly higher in the doxorubicin-treated groups (1.0 and 3.0 µg/mL) than in the controls at 12 and 24 h. In conclusion, VSIG4 expression was upregulated in the UUO and doxorubicin-induced kidney injury models. VSIG4 may be involved in pathogenesis and disease progression in chronic kidney disease models.

Role of NADPH Oxidases in Renal Aging.

INTRODUCTION: Aging of the kidney is associated with complex molecular, histological, and functional changes. Although the aging process itself does not induce renal damage, underlying disease such as diabetes mellitus can aggravate kidney injury during aging. Although oxidative stress is considered an important mediator in age-related renal fibrosis, it is unclear how oxidative stress increases during normal and diabetic aging. METHODS: In this study, we investigated molecular changes in the kidney in normal and diabetic aging mice. C57BL/6 mice were studied at 2, 12, and 24 months of age, and leptin receptor-deficient db/db mice were studied at 8, 12, 16, 20, 24, and 38 weeks of age. We measured renal functional parameters, fibrotic and inflammatory markers, and oxidative stress markers at all the above time points. RESULTS: Both nondiabetic and diabetic mice exhibited progressive microalbuminuria during their lifespan. Interestingly, both diabetic aging and normal aging mice showed progressive increases in oxidative stress markers such as plasma and urinary 8-isoprostane, as well as renal lipid hydroperoxide content. In renal tissues, proinflammatory and profibrotic molecules were significantly upregulated in an age-dependent manner. Expression of three NADPH oxidase (Nox) isoforms, namely, Nox1, Nox2, and Nox4, was significantly increased during aging. Compared with normal aging mice, diabetic db/db mice demonstrated more dramatic changes during aging process. CONCLUSIONS: Our findings suggest that NADPH oxidases play an important role in the aging kidney under both normal and diabetic conditions. Targeting of these oxidases might be a new promising therapy to treat issues associated with aging kidneys.

The FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial.

As angiotensin II type 1 receptor blockers (ARBs) may have different antiproteinuric effects in diabetic kidney disease (DKD), we ascertained the albuminuria-reducing effect of fimasartan and losartan in patients with DKD. This was a randomized, multicenter, double-blind, 4-parallel-group, dose-titration, phase III study designed to compare the efficacy of fimasartan and losartan in reducing albuminuria in patients with DKD (NCT02620306). The primary endpoint was the rate of change in albuminuria from baseline to week 24. A total of 341 patients were randomized to different groups. The urinary albumin-to-creatinine ratio (ACR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were not different between the fimasartan and losartan groups at baseline (ACR: 1376.84 vs. 1521.07 mg/gCr, SBP: 154.69 vs. 154.47 mmHg, DBP: 83.96 vs. 83.83 mmHg). However, ACR reduction was significantly larger in the fimasartan group than in the losartan group during the entire study period (% changes in the ACR at 4, 8, 12, and 24 weeks were -23.58, -33.06, -35.00, and -38.13 in the fimasartan group vs. -8.74, -10.17, -14.91, and -19.71 in the losartan group, p < 0.01, respectively). The superior antiproteinuric effect of fimasartan compared to losartan was still significant after adjustment for SBP levels. There were no significant differences in adverse events, including the incidences of estimated glomerular filtration decline and hyperkalemia. This study demonstrates that compared to losartan, fimasartan significantly reduces albuminuria in patients with DKD, even after adjustment for SBP and DBP.

Association between depressive symptoms and bone density in elderly patients with non-dialysis dependent chronic kidney disease.

BACKGROUND: Depression is a disease that is commonly accompanied by elderly chronic kidney disease (CKD) patients, but when the two diseases are accompanied, etiology or combination are not well known. We aimed to evaluate the etiology of CKD and comorbid depression by investigating bone disorders that are observed in persons affected by both CKD and depression. METHODS: We conducted a cross-sectional study with a total of 646 patients with CKD. We compared the sociodemographic factors, kidney function, markers for CKD-Mineral and Bone Disorder (CKD-MBD) and bone mineral density according to the depressive symptoms. We conducted a univariate and multivariate logistic regression analysis to calculate odd ratios (95 % confidence interval) between depressive symptoms and low bone mineral density. RESULTS: Individuals with CKD and depressive symptoms were associated with lower level of education attained, living alone, exercising less, low 24-hour urine phosphorus, and low bone density. Depressive symptoms were significantly associated with low bone density in lowest parts (1.55 [1.06-2.29]) and in total hip (1.72 [1.17-2.53]) even after adjusting for diabetes mellitus, hypertension, kidney function, proteinuria, age, sex, smoking, and body mass index. LIMITATIONS: A cross-sectional design was used in this study and the bone biopsy for diagnosis of CKD-MBD was not done because of invasiveness and practical difficulties. CONCLUSION: Low bone density was associated with depressive symptoms in elderly patients with non-dialysis chronic kidney disease.

Upregulation of VSIG4 in Type 2 Diabetic Kidney Disease.

Fibrosis is the final common finding in patients with advanced diabetic kidney disease. V-set Ig domain containing 4 (VSIG4) is related to fibrosis in several diseases. It also contributes to fibrosis under high-glucose conditions in renal tubule cells. To determine the role of VSIG4 in type 2 diabetes, we examined VSIG4 expression in a type 2 diabetic animal model and podocyte. Urinary excretion of albumin and VSIG4 was significantly higher in db/db mice than in the control group. Urine VSIGs levels for 6 h were about three-fold higher in db/db mice than in db/m mice at 20 weeks of age: 55.2 ± 37.8 vs. 153.1 ± 74.3 ng, p = 0.04. Furthermore, urinary VSIG4 levels were significantly correlated with urinary albumin levels (r = 0.77, p < 0.01). Intrarenal VSIG4 mRNA expression was significantly higher in db/db mice than in control mice (1.00 ± 0.35 vs. 1.69 ± 0.77, p = 0.04). Further, VSIG4 expression was almost twice as high in db/db mice at 20 weeks of age. Intrarenal VSIG immunoreactivity in db/db mice was also significantly higher than that in control mice. In cultured podocytes, both high glucose and angiotensin II significantly upregulated the expression of VSIG4 mRNA and protein. In conclusion, VSIG4 was upregulated in an animal model of type 2 diabetes and was related to albuminuria and pro-fibrotic markers. Considering these relationships, VSIG4 may be an important mediator of diabetic nephropathy progression.

A Case Report of MPO-ANCA-Associated Vasculitis Following Heterologous mRNA1273 COVID-19 Booster Vaccination.

Despite that clinical trials have been examining the safety profile of coronavirus disease 2019 (COVID-19) vaccines, there are concerns about long-term side effects as the number of vaccinations increases. Herein, we report a case of new-onset renal-limited anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis after booster vaccination with the mRNA 1273 (Moderna) vaccine. A 72-year-old woman with no specific past history, and who had a normal renal function, developed ANCA-associated vasculitis following heterologous booster with mRNA1273 (Moderna) vaccine. After a kidney biopsy, she was diagnosed with ANCA-associated pauci-immune crescentic glomerulonephritis. Her renal function and constitutional symptoms have been improved with treatment with plasmapheresis, intravenous cyclophosphamide and steroid pulse therapy (intravenous 500 mg of methylprednisolone sodium succinate for 3 days) followed by a reduced steroid regimen.

Associations between local acidosis induced by renal LDHA and renal fibrosis and mitochondrial abnormalities in patients with diabetic kidney disease.

During the progression of diabetic kidney disease (DKD), renal lactate metabolism is rewired. The relationship between alterations in renal lactate metabolism and renal fibrosis in patients with diabetes has only been partially established due to a lack of biopsy tissues from patients with DKD and the intricate mechanism of lactate homeostasis. The role of lactate dehydrogenase A (LDHA)-mediated lactate generation in renal fibrosis and dysfunction in human and animal models of DKD was explored in this study. Measures of lactate metabolism (urinary lactate levels and LDHA expression) and measures of DKD progression (estimated glomerular filtration rate and Wilms' tumor-1 expression) were strongly negatively correlated in patients with DKD. Experiments with streptozotocin-induced DKD rat models and the rat renal mesangial cell model confirmed our findings. We found that the pathogenesis of DKD is linked to hypoxia-mediated lactic acidosis, which leads to fibrosis and mitochondrial abnormalities. The pathogenic characteristics of DKD were significantly reduced when aerobic glycolysis or LDHA expression was inhibited. Further studies will aim to investigate whether local acidosis caused by renal LDHA might be exploited as a therapeutic target in patients with DKD.

A multicenter, randomized, open-label, comparative, phase IV study to evaluate the efficacy and safety of combined treatment with mycophenolate mofetil and corticosteroids in advanced immunoglobulin A nephropathy.

BACKGROUND: It remains unclear whether immunosuppressive agents are effective in patients with immunoglobulin A nephropathy (IgAN). We investigated the efficacy of a mycophenolate mofetil (MMF) and corticosteroid combination therapy in patients with advanced IgAN. METHODS: We conducted a multicenter, randomized, placebo-controlled, parallel-group study of 48 weeks administration of MMF and corticosteroids in biopsy-proven advanced IgAN patients with estimated glomerular filtration rate (eGFR) of 20-50 mL/min/1.73 m2 and urine protein-to-creatinine ratio (UPCR) of >0.75 g/day. The primary outcome was complete (UPCR < 0.3 g/day) or partial (>50% reduction of UPCR compared to baseline) remission at 48 weeks. RESULTS: Among the 48 randomized patients, the percentage that achieved complete or partial remission was greater in the combination therapy group than in the control group (4.2% vs. 0% and 29.1% vs. 5.0%, respectively). Compared with the combination therapy group, eGFR in the control group decreased significantly from week 36 onward, resulting in a final adjusted mean change of -4.39 ± 1.22 mL/min/1.73 m2 (p = 0.002). The adjusted mean changes after 48 weeks were 0.62 ± 1.30 and -5.11 ± 1.30 mL/min/1.73 m2 (p = 0.005) in the treatment and control groups, respectively. The UPCR was significantly different between the two groups; the adjusted mean difference was -0.47 ± 0.17 mg/mgCr and 0.07 ± 0.17 mg/mgCr in the treatment and control group, respectively (p = 0.04). Overall adverse events did not differ between the groups. CONCLUSION: In advanced IgAN patients with a high risk for disease progression, combined MMF and corticosteroid therapy appears to be beneficial in reducing proteinuria and preserving renal function.

Differences in estimated glomerular filtration rate are associated with different patterns of 24-h ambulatory blood pressure in the general population.

BACKGROUND: Alterations of the circadian blood pressure rhythm are associated with cardiovascular and chronic kidney diseases. We investigated the relationship between 24-h ambulatory blood pressure monitoring (ABPM) patterns and eGFR differences in participants without chronic kidney disease. METHOD: This cross-sectional study was conducted using data from the ongoing Korean Genome and Epidemiology Study, which involves 1733 participants (age, 60 ±â€Š7 years; 938 women) with an eGFR >60 ml/min per 1.73 m2. The blood pressure dipping status was stratified as reverse-dipper (<0%), nondipper (0 to <10%), and dipper (≥10%). They were also categorized into eGFR quartiles (Q4, 128.6-101.6; Q3, 101.5-95.7; Q2, 95.6-87.4; and Q1, 87.3-60.5), and Q4 was fixed as the reference. RESULTS: The proportion of dippers progressively decreased and the proportions of reverse and nondippers significantly increased from the highest to the lowest eGFR quartile (P < 0.001). In the univariate analyses, the Q1 and Q2 groups were significantly associated with increasing odds ratios (ORs) for the nondipper, reverse-dipper, and nondipper plus reverse-dipper groups. After adjustment, the lowest eGFR group was significantly associated with the reverse-dipper and nondipper plus reverse-dipper patterns in comparison with the highest eGFR group [OR = 1.685, 95% confidence interval (CI), 1.002-2.834; OR = 1.422, 95% CI, 1.023-1.978, respectively). The significant linear trend for an association of the nondipper plus reverse-dipper pattern with a decrease in eGFR was confirmed with the test for trend (P = 0.023). CONCLUSION: Differences in eGFR are associated with different 24-h ABPM patterns in non-CKD individuals. ABPM can identify individuals with a nondipper status in this population.

Lower response to denosumab in diabetes patients on hemodialysis.

INTRODUCTION: The incidence of fractures is much higher in patients with chronic kidney disease, especially those on hemodialysis (HD). Denosumab is known to treat osteoporosis. However, no exact guideline exists for treatment with denosumab in patients, especially those with diabetes. This study analyzed the effect of denosumab in HD patients with or without diabetes. MATERIALS AND METHODS: Dual-energy X-ray absorptiometry was performed in 89 HD patients: 42 were diagnosed with osteoporosis. 33 patients were treated with denosumab. An observational retrospective analysis was conducted in 25 HD patients whose follow-up biomarkers were measured at 6 months after denosumab treatment. FINDINGS: Bone mineral density (BMD) of lumbar spine (LS) and femur neck (FN) were largely improved (+3.40% and 4.96%, respectively) 1 year after the treatment. The T-scores were also improved. Both bone turnover markers were significantly decreased 6 months after treatment; the levels of C-terminal telopeptide (CTX) and bone-specific alkaline phosphatase (bsALP) were decreased by -1.04 ± 1.24 ng/mL (p < 0.001) and -35.72 ± 36.07 IU/L (p < 0.001), respectively. The response was significantly different between the diabetes and non-diabetes group. The increase in LS BMD was significantly lower in the diabetes group than in the non-diabetes group (0.02 ± 0.03 vs. 0.07 ± 0.02, p = 0.02). Decrease in CTX, but not in bsALP, was also lower in the diabetes group compared to the non-diabetes group (-0.58 ± 0.70 vs. -1.55 ± 1.12, p = 0.03). Pretreatment with calcium and calcitriol prevented symptomatic hypocalcemia except in 1 case. CONCLUSION: Denosumab improved bone density and osteoclastic activity in HD patients, with a lower response in patients with diabetes.

Blood Pressure Control in Patients with Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease. Blood pressure (BP) control can reduce the risks of cardiovascular (CV) morbidity, mortality, and kidney disease progression. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines have suggested the implementation of a more intensive BP control with a target systolic BP (SBP) of <120 mmHg based on the evidence that the CV benefits obtained is outweighed by the kidney injury risk associated with a lower BP target. However, an extremely low BP level may paradoxically aggravate renal function and CV outcomes. Herein, we aimed to review the existing literature regarding optimal BP control using medications for DKD.