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Sarcopenia is a condition characterized by a loss of muscle mass and function. In chronic kidney disease (CKD), where a chronic catabolic state exists, sarcopenia commonly occurs through various mechanisms, resulting in muscle wasting and decreased muscle endurance. Sarcopenic patients with CKD have high morbidity and mortality rates. Indeed, the prevention and treatment of sarcopenia are mandatory. An imbalance between protein synthesis and degradation in muscle and increased oxidative stress and inflammation persist in CKD and induce muscle wasting. In addition, uremic toxins negatively affect muscle maintenance. A variety of potential therapeutic drugs targeting these muscle-wasting mechanisms in CKD have been investigated, but most of the trials focused on aged patients without CKD, and none of these drugs have been approved for the treatment of sarcopenia so far. Further studies on the molecular mechanisms of sarcopenia in CKD and targets for potential therapeutics are needed to improve the outcomes of sarcopenic patients with CKD.
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Immunoglobulin A nephropathy (IgAN) is the most prevalent form of glomerulonephritis worldwide. Prediction of disease progression in IgAN can help to provide individualized treatment based on accurate risk stratification. Methods: We performed proton nuclear magnetic resonance-based metabolomics analyses of serum and urine samples from healthy controls, non-progressor (NP), and progressor (P) groups to identify metabolic profiles of IgAN disease progression. Metabolites that were significantly different between the NP and P groups were selected for pathway analysis. Subsequently, we analyzed multivariate area under the receiver operating characteristic (ROC) curves to evaluate the predictive power of metabolites associated with IgAN progression. Results: We observed several distinct metabolic fingerprints of the P group involving the following metabolic pathways: glycolipid metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-transfer RNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism. In multivariate ROC analyses, the combinations of serum glycerol, threonine, and proteinuria (area under the curve [AUC], 0.923; 95% confidence interval [CI], 0.667–1.000) and of urinary leucine, valine, and proteinuria (AUC, 0.912; 95% CI, 0.667–1.000) showed the highest discriminatory ability to predict IgAN disease progression. Conclusion: This study identified serum and urine metabolites profiles that can aid in the identification of progressive IgAN and proposed perturbed metabolic pathways associated with the identified metabolites.
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Parathyroid carcinoma (PC) in cases of secondary or tertiary hyperparathyroidism is relatively uncommon, and only a few case reports have described this entity. Although some papers have reported patients with one or two parathyroid malignancies, multiple PC–especially three or more–have been even more rarely reported. Herein, we report a case of secondary hyperparathyroidism due to multiple PCs in a chronic hemodialysis patient. A 54-year-old man with end-stage kidney disease was referred for hyperparathyroidism. He had been diagnosed with chronic kidney disease in 2001 and had begun hemodialysis in 2009. In laboratory tests, intact parathyroid hormone (iPTH) was markedly elevated to 1,144.1 pg/mL (normal range: 15.0–68.3 pg/mL) and serum calcium was mildly elevated to 10.56 mg/dL (normal range: 8.5–10.3 mg/dL). Ultrasonography showed hypoechoic nodules in the posterior part of both thyroid glands. All three nodules showed increased uptake on a 99mTc sestamibi scan. The patient underwent total parathyroidectomy with autotransplantation to the right forearm. Histopathology findings showed three PCs with capsular invasion and one parathyroid hyperplasia. In the immediate postoperative period, the iPTH level dropped from 1,446.8 to 82.4 pg/dL and, after 1 month, to 4.0 pg/dL. This patient needed oral calcium carbonate and active vitamin D to maintain appropriate serum calcium levels. Although multiple PCs are rare, they can cause secondary hyperparathyroidism. Therefore, clinicians should suspect multiple PCs when patients’ serum iPTH levels are exceptionally high. Additionally, since PCs could occur in multiple glands, autotransplantation of the parathyroid gland after parathyroidectomy should be done carefully.
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Whether continuous renal replacement therapy (CRRT) should be applied to critically ill patients with both acute kidney injury (AKI) and cancer remains controversial because of poor expected outcomes. The present study determined prognostic factors for all-cause in-hospital mortality in patients with AKI and cancer undergoing CRRT. Methods: We included 471 patients with AKI and cancer who underwent CRRT at the intensive care unit of a Korean tertiary hospital from 2013 to 2020, and classified them by malignancy type. The primary outcomes were 28-day all-cause mortality rate and prognostic factors for in-hospital mortality. The secondary outcome was renal replacement therapy (RRT) dependency at hospital discharge. Results: The 28-day mortality rates were 58.8% and 82% in the solid and hematologic malignancy groups, respectively. Body mass index (BMI), presence of oliguria, Sequential Organ Failure Assessment (SOFA) score, and albumin level were common predictors of 28-day mortality in the solid and hematologic malignancy groups. A high heart rate and the presence of severe acidosis were prognostic factors only in the solid malignancy group. Among the survivors, the proportion with RRT dependency was 25.0% and 33.3% in the solid and hematologic malignancy groups, respectively. Conclusion: The 28-day mortality rate of cancer patients with AKI undergoing CRRT was high in both the solid and hematologic malignancy groups. BMI, presence of oliguria, SOFA score, and albumin level were common predictors of 28-day mortality in the solid and hematologic malignancy groups, but a high heart rate and severe acidosis were prognostic factors only in the solid malignancy group.
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Background@#We aimed to investigate the clinical characteristics and outcomes of patients aged ≥65 years with antineutrophil cytoplasmic autoantibody (ANCA)-positive ANCA-associated vasculitis (AAV) in Korea. @*Methods@#Seventy patients diagnosed with ANCA-positive AAV from 2006 to 2019 at a single center were analyzed and categorized into younger (aged <65 years) or elderly (aged ≥65 years) groups. Initial induction treatments were investigated according to age group. All-cause mortality and kidney outcomes were evaluated. @*Results@#After categorization by age, 34 (48.6%) and 36 patients (51.4%) were in the younger and elderly groups, respectively. In the elderly group, more patients were treated with oral cyclophosphamide (CYC) (30.6%) than with intravenous CYC (19.4%). During a median follow-up of 14.6 months (range, 3.0-53.1 months), 13 patients died (elderly group: 11 patients, 84.6%). In the elderly group, older age (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09-1.90; p = 0.01), lower hemoglobin (HR, 0.21; 95% CI, 0.08-0.60; p = 0.003), and higher serum creatinine level (HR 14.17; 95% CI, 1.29-155.84; p = 0.03) were significant risk factors for all-cause mortality after adjustment. Oral CYC + steroid treatment was associated with decreased all-cause mortality compared to untreated induction immunosuppressants (HR, 0.01; 95% CI, 0.0003-0.47; p = 0.02). Kidney failure or renal recovery outcomes were not significantly different between the younger and elderly groups. @*Conclusion@#Patients aged ≥65 years had higher mortality rates than younger patients, and mortality was associated with older age, lower hemoglobin, higher serum creatinine level, and nontreatment compared to oral CYC + steroids.
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Evidence of the ethical appropriateness and clinical benefits of shared decision-making (SDM) are accumulating. This study aimed to not only identify physicians’ perspectives on SDM, and practices related to end-of-life care in particular, but also to gauge the effect of SDM education on physicians in Korea. Methods: A 14-item questionnaire survey using a modified Delphi process was delivered to nephrologists and internal medicine trainees at 17 university hospitals. Results: A total of 309 physicians completed the survey. Although respondents reported that 69.9% of their practical decisions were made using SDM, 59.9% reported that it is not being applied appropriately. Only 12.3% of respondents had received education on SDM as part of their training. The main obstacles to appropriate SDM were identified as lack of time (46.0%), educational materials and tools (29.4%), and education on SDM (24.3%). Although only a few respondents had received training on SDM, the proportion of those who thought they were using SDM appropriately in actual practice was high; the proportion of those who chose lack of time and education as factors that hindered the proper application of SDM was low. Conclusion: The majority of respondents believed that SDM was not being implemented properly in Korea, despite its use in actual practice. To improve the effectiveness of SDM in the Korean medical system, appropriate training programs and supplemental policies that guarantee sufficient application time are required.
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Diabetes has reached epidemic proportions, both in Korea and worldwide and is associated with an increased risk of chronic kidney disease and kidney failure (KF). The natural course of kidney function among people with diabetes (especially type 2 diabetes) may be complex in real-world situations. Strong evidence from observational data and clinical trials has demonstrated a consistent association between decreased estimated glomerular filtration rate (eGFR) and subsequent development of hard renal endpoints (such as KF or renal death). The disadvantage of hard renal endpoints is that they require a long follow-up duration. In addition, there are many patients with diabetes whose renal function declines without the appearance of albuminuria, measurement of the eGFR is emphasized. Many studies have used GFR-related parameters, such as its change, decline, or slope, as clinical endpoints for kidney disease progression. In this respect, understanding the trends in GFR changes could be crucial for developing clinical management strategies for the prevention of diabetic complications. This review focuses on the clinical implication of the eGFR-related parameters that have been used so far in diabetic kidney disease. We also discuss the use of recently developed new antidiabetic drugs for kidney protection, with a focus on the GFR as clinical endpoints.
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Background@#Phosphorus-containing dialysis solution is used to prevent hypophosphatemia in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). This study evaluated the effect of phosphorus-containing dialysis solution on mortality in patients undergoing CVVHDF based on changes in phosphorus and red cell distribution width-coefficient of variation (RDW-CV) levels. @*Methods@#We included 272 patients with acute kidney injury (AKI) who underwent CVVHDF at the medical intensive care unit from 2017 to 2019 and classified them according to Phoxilium (Baxter Healthcare Ltd.), as a phosphorus-containing dialysis solution, use within 48 hours after CVVHDF initiation. Clinical data were collected at baseline and 48 hours after CVVHDF initiation. The primary outcome was all-cause mortality during the follow-up period. @*Results@#The non-Phoxilium (NP) group had higher phosphorus and lower RDW-CV levels than the Phoxilium (P) group (phosphorus, 7.3 ± 4.3 vs. 5.0 ± 2.8 mg/dL; RDW-CV, 14.6 ± 1.9 vs. 15.7 ± 2.6%; all p 0 mg/dL vs. 0% vs. 0% vs. >–0.2% and <0%; HR, 2.65; 95% CI, 1.12–6.24; p = 0.03), while an increase in delta phosphorus was not. @*Conclusion@#In patients with AKI undergoing CVVHDF, the risk factors for all-cause mortality differed according to the initial phosphorus levels and use of Phoxilium.
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Background@#Data on liver cirrhosis (LC) patients undergoing continuous renal replacement therapy (CRRT) are lacking despite 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 factors predictive 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 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.
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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-β1 (TGF-β1)/Smad signaling compared with WT sham mice. However, TGF-β1/Smad expression did not differ between the two groups. The levels of phosphorylated GSK-3β, β-catenin, and Snail were attenuated in Akt1−/− UIRI mice compared with those in WT UIRI mice. @*Conclusions@#Deletion of Akt1 results in the attenuation of renal fibrosis and tubular dedifferentiation, independent of TGF-β1/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.
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Objective@#The purpose of this study is to examine the effect of high mobility group AT-hook 1 (HMGA1) on the phenotyptic change of vascular smooth muscle cells (VSMCs). @*Methods@#Gene silencing and overexpression of HMGA1 were introduced to evaluate the effect of HMGA1 expression on the phenotypic change of VSMCs. Marker gene expression of VSMCs was measured by promoter assay, quantitative polymerase chain reaction, and western blot analysis. Common left carotid artery ligation model was used to establish in vivo neointima formation. @*Results@#HMGA1 was expressed strongly in the synthetic type of VSMCs and significantly downregulated during the differentiation of VSMCs. Silencing of HMGA1 in the synthetic type of VSMCs enhanced the expression of contractile marker genes thereby enhanced angiotensin II (Ang II)-dependent contraction, however, significantly suppressed proliferation and migration. Stimulation of contractile VSMCs with platelet-derived growth factor (PDGF) enhanced HMGA1 expression concomitant with the downregulation of marker gene expression which was blocked significantly by the silencing of HMGA1. Silencing of HMGA1 retained the Ang II-dependent contractile function, which was curtailed by PDGF stimulation, however, overexpression of HMGA1 in the contractile type of VSMCs suppressed marker gene expression. Proliferation and migration were enhanced significantly by the overexpression of HMGA1. Furthermore, the Ang II-dependent contraction was reduced significantly by the overexpression of HMGA1. Finally, the expression of HMGA1 was enhanced significantly in the ligated artery, especially in the neointima area. @*Conclusion@#HMGA1 plays an essential role in the phenotypic modulation of VSMCs.Therefore, paracrine factors such as PDGF may affect vascular remodeling through the regulation of HMGA1.
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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-β1 (TGF-β1)/Smad signaling compared with WT sham mice. However, TGF-β1/Smad expression did not differ between the two groups. The levels of phosphorylated GSK-3β, β-catenin, and Snail were attenuated in Akt1−/− UIRI mice compared with those in WT UIRI mice. @*Conclusions@#Deletion of Akt1 results in the attenuation of renal fibrosis and tubular dedifferentiation, independent of TGF-β1/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.
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Purpose@#Fatigue breakage of cortical screws sometimes occurs after syndesmosis fixation, regardless of the period of screw retention. This study compared the fatigue strength of a novel screw design to conventional cortical screws in the fixed state of syndesmosis. @*Materials and Methods@#Twelve sawbone models were tested mechanically to determine the fatigue strength of three screw designs. The first group was composed of cortical screws, while the second and third groups were newly-designed screws. The second group was composed of screws with a 2.4-mm diameter thread-free portion of the mid-shank while the third group had a 2.0-mm diameter threadfree mid-shank. A 400 N load was applied repetitively to a fibula model and the number of cycles until screw failure was recorded. Four screws from each group were tested, giving a total of 12 fatigue tests. @*Results@#The average cycles until screw failure for groups 1, 2, and 3 were 8,134, 63,186, and 2,581, respectively. The second group showed the highest fatigue strength (p=0.018). The other two screw designs showed similar fatigue strength (p=0.401). @*Conclusion@#New screw designs with a thread-free portion in the mid-shank could reduce the occurrence of fatigue breakage after syndesmosis fixation.
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Background@#Urgent-start peritoneal dialysis (PD) is applied to patients who need PD within two weeks but are able to wait for more than 48 hours before starting PD. To evaluate the usefulness of percutaneous PD catheter insertion in urgent-start PD, we reviewed the clinical outcomes of percutaneous catheter insertion with immediate start PD and surgical insertion with longer break-in time in Pusan National University Hospital. @*Methods@#This study included 177 patients who underwent urgent-start PD. Based on the PD catheter insertion techniques, the patients with urgent-start PD were divided into percutaneous (n = 103) and surgical (n = 74) groups. For the percutaneous group, a modified Seldinger percutaneous catheter insertion with immediate initiation of continuous ambulatory PD was performed by nephrologists. @*Results@#The percutaneous group showed higher serum urea nitrogen, creatinine, and lower serum albumin compared with the surgical group (P < 0.05). Ninety-day infectious and mechanical complications showed no significant differences between the two groups. Ninety-day peritonitis in the percutaneous group was 9.7% compared to 5.4% in the surgical group (P = not significant [NS]). Major leakage was 3.9% in the percutaneous group compared to 1.4% in the surgical group (P = NS). Overall infectious and mechanical complication-free survival was not significantly different between the two groups. The percutaneous group and surgical group showed no statistical difference with respect to catheter survival over the entire observation period (P = NS). @*Conclusion@#This study suggests that urgent-start PD can be applied safely with percutaneous catheter insertion by nephrologists with no break-in period.
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BACKGROUND: Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.METHODS: Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.RESULTS: In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.CONCLUSION: Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.
Subject(s)
Female , Humans , Adipose Tissue , Apolipoproteins , Body Composition , Body Weight , Clusterin , Diabetes Mellitus, Type 2 , Exercise , Insulin Resistance , Insulin , Muscle, Skeletal , SarcopeniaABSTRACT
BACKGROUND/AIMS@#Little is known about tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity in human immunodeficiency virus (HIV)-infected patients in Korea. The objective of this study was to evaluate the incidence and risk factors of TDF-associated nephrotoxicity among HIV-infected patients in Korea.@*METHODS@#A single-center retrospective cohort study was conducted on HIV-infected patients in Korea. We included patients who had started TDF or abacavir (ABC)-based antiretroviral therapy (ART) between October 2006 and December 2014. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease-Epidemiology Collaboration equation. Renal dysfunction was defined as > 25% decrease of baseline eGFR. A propensity matched case-control study was conducted to compare renal dysfunction rates between the two groups. The risk factors of nephrotoxicity were analyzed by Cox regression analysis.@*RESULTS@#A total of 210 HIV-infected patients were included in the study, of which, 108 were TDF-based ART group and 102 were ABC-based ART group. Renal dysfunction occurred in 16 patients (14.8%) in the TDF group and 11 (10.8%) in the ABC group. Incidence of renal dysfunction of TDF and ABC group was 9.66 per 100 person-years (PYs) and 5.14 per 100 PYs, respectively (p = 0.176). In propensity-score-matched analysis, renal dysfunction rates were TDF 13.3% versus ABC 13.3% (p > 0.999). In multivariable analysis, Centers for Disease Control and Prevention clinical category C was a significant risk factor for renal dysfunction.@*CONCLUSIONS@#Approximately, 13% of HIV-infected patients treated with TDF had renal dysfunction. Advanced stage of HIV infection was a significant risk factor for renal dysfunction.
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BACKGROUND: This study was undertaken to explore the effects of aging on the kidneys in mouse models of diabetes and chronic kidney disease (CKD), and to compare the expression of two isoforms of matrix metalloproteinase-2 (MMP-2)–secretory full-length MMP-2 and intracellular N-terminal truncated MMP-2 (NTT-MMP-2)–in these models. METHODS: Two experimental ICR mouse models were used: a streptozotocin (STZ)-induced type 1 diabetes mellitus model and a 5/6 nephrectomized (5/6Nx) CKD model. The abundance of each isoform of MMP-2 was determined by quantitative polymerase chain reaction (qPCR), and functional analyses were conducted. Moreover, the protein levels of the two MMP-2 isoforms were determined semi-quantitatively by immunohistochemical staining, and their association with tissue damage was assessed. RESULTS: Both isoforms of MMP-2 were upregulated in the kidney tissues of STZ-induced diabetic mice and 5/6Nx mice, irrespective of age. Characteristically, NTT-MMP-2 protein expression was elevated in old control mice, in line with the qPCR results. NTT-MMP-2 expression was limited to the renal cortex, and to the tubulointerstitial area rather than the glomerular area. In terms of tissue damage, tubulointerstitial fibrosis was more severe in old 5/6Nx mice than in their young counterparts, whereas glomerulosclerosis was comparable in old and young 5/6Nx mice. CONCLUSION: The intracellular isoform of MMP-2 was induced by ageing, irrespective of the presence of diabetes or CKD, and its induction may be related to tubulointerstitial fibrosis in chronic kidney disease.
Subject(s)
Animals , Mice , Aging , Diabetes Mellitus , Diabetes Mellitus, Type 1 , Fibrosis , Kidney , Matrix Metalloproteinase 2 , Mice, Inbred ICR , Polymerase Chain Reaction , Protein Isoforms , Renal Insufficiency, Chronic , StreptozocinABSTRACT
Urinary angiotensinogen (AGT) is potentially a specific biomarker for the status of the intrarenal renin-angiotensin system (RAS) in patients with diabetes mellitus. We explored whether changes in urinary AGT excretion levels were associated with the deterioration of kidney function in type 2 diabetes patients with preserved kidney function. Urinary baseline AGT levels were measured in 118 type 2 diabetic patients who were not taking RAS blockers and who had estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m². A total of 91 patients were followed-up for 52 months. Changes in urinary levels of AGT (ΔAGT) were calculated by subtracting urinary AGT/creatinine (Cr) at baseline from urinary AGT/Cr after 1 year. ΔAGT was significantly inversely correlated with annual eGFR change (β = −0.29, P = 0.006; β = −0.37, P = 0.001 after adjusting for clinical factors). RAS blockers were prescribed in 36.3% of patients (n = 33) during follow-up. The ΔAGT values were lower in the RAS blockers users than in the non-RAS blockers users, but the differences were not statistically significant (7.37 ± 75.88 vs. 22.55 ± 57.45 μg/g Cr, P = 0.081). The ΔAGT values remained significantly correlated with the annual rate of eGFR change (β = −0.41, P = 0.001) in the patients who did not use RAS blockers, but no such correlation was evident in the patients who did. ΔAGT is inversely correlated with annual changes in eGFR in type 2 diabetes patients with preserved kidney function, particularly in RAS blocker-naïve patients.