Subject(s)
Albuminuria , Glomerular Filtration Rate , Renal Insufficiency , Acute Disease , Albuminuria/etiology , Humans , Renal Insufficiency/complications , Renal Insufficiency/physiopathology , Renal Insufficiency/urine , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/urineABSTRACT
INTRODUCTION: Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important. AIMS: Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction. METHODS: WKF was defined as a ≥40% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR <15 mL/min, or dialysis. Mixed-effects and time-updated Cox models were used. RESULTS: 5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a p value ≤0.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06-7.96), p value <0.0001. CONCLUSION: Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality.
Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/blood , Diabetic Nephropathies/urine , Kidney/physiopathology , Renal Insufficiency/blood , Renal Insufficiency/urine , Acute Coronary Syndrome/complications , Aged , Biomarkers/blood , Biomarkers/urine , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/complications , Diabetic Nephropathies/physiopathology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Renal Insufficiency/complications , Renal Insufficiency/physiopathology , Symptom Flare UpABSTRACT
The intent of this study was to ascertain the prevalence of augmented renal clearance (ARC) in patients with traumatic injuries who require nutrition therapy and identify factors associated with ARC. Adult patients admitted to the trauma intensive care unit from January 2015 to September 2016 who received enteral or parenteral nutrition therapy and had a 24 h urine collection within 4 to 14 days after injury were retrospectively evaluated. Patients with a serum creatinine concentration > 1.5 mg/dL, required dialysis, or had an incomplete urine collection were excluded. ARC was defined as a measured creatinine clearance > 149 mL/min/1.73 m2. Two hundred and three patients were evaluated. One hundred and two (50%) exhibited ARC. A greater proportion of patients with ARC were male (86% vs. 67%; p = 0.004), had traumatic brain injury (33% vs. 9%; p = 0.001), a higher injury severity score (30 ± 11 vs. 26 ± 12; p = 0.015), were younger (36 ± 15 vs. 54 ± 17 years; p = 0.001), had a lower serum creatinine concentration (0.7 ± 2 vs. 0.9 ± 0.2 mg/dL; p = 0.001) and were more catabolic (nitrogen balance of -10.8 ± 13.0 vs. -6.2 ± 9.2 g/d; p = 0.004). The multivariate analysis revealed African American race and protein intake were also associated with ARC. Half of critically ill patients with traumatic injuries experience ARC. Patients with multiple risk factors for ARC should be closely evaluated for dosing of renally-eliminated electrolytes, nutrients, and medications.
Subject(s)
Critical Illness/therapy , Nutrition Therapy , Renal Insufficiency/complications , Renal Insufficiency/diet therapy , Adult , Aged , Brain Injuries , Brain Injuries, Traumatic , Creatinine/blood , Female , Humans , Intensive Care Units , Kidney , Male , Middle Aged , Multivariate Analysis , Nutritional Support , Obesity , Prevalence , Renal Dialysis , Renal Elimination , Renal Insufficiency/urine , Retrospective Studies , Risk FactorsABSTRACT
Objectives: The present study aimed to observe the differences in creatinine clearance (Ccr) in systemic lupus erythematosus (SLE) patients with normal serum creatinine at different levels of urinary protein. Method: The present cross-sectional study included 177 SLE patients with normal serum creatinine from Qilu Hospital of Shandong University between January 2010 and April 2020. The following data were collected: blood urea nitrogen (BUN), serum creatinine (Cr), serum total protein, serum albumin, immunoglobulin (Ig) G, IgA, IgM, complement 3, complement 4, anti-ds-DNA antibody, routine urine test, urine protein/creatinine ratio (UPCR) (g/g), and the SLE disease activity index. The estimated Ccr was calculated according to the Cockcroft formula. Results: 123 patients were with positive urinary protein (Lupus Nephritis, LN group) and 54 patients were with negative urinary protein (Non-LN group). Compared with the Non-LN group, the LN group had higher BUN (5.76±3.22 vs. 4.78±1.58, P=0.007) and Cr (62.36±19.53 vs. 54.83±11.09, P=0.001). There was a strong correlation between the UPCR and the semi-quantitative determination of urine protein in LN patients (r=0.9583, P=0.0417). The serum creatinine levels were significantly higher in patients with urine protein 3+ (72.97±25.16) or massive proteinuria (62.32±19.66) than the other groups. Patients with urinary protein ± exhibited a significantly elevated Ccr when compared to patients with urinary protein 3+ (130.6±44.15 vs. 110.5±33.50, P=0.02), and patients with UPCR<0.15 g/g had higher Ccr than other groups and showed significantly increased Ccr compared with patients with UPCR≥0.15 g/g (132.44±21.02 vs. 115.14±35.89, P=0.007). Conclusions: Early renal function impairment may be present in LN patients. The kidneys of LN patients with urinary protein ± or UPCR<0.15 g/g are in a state of hyperfunction.
Subject(s)
Creatinine/metabolism , Kidney/physiopathology , Lupus Nephritis/complications , Renal Elimination/physiology , Renal Insufficiency/physiopathology , Adult , Creatinine/blood , Creatinine/urine , Cross-Sectional Studies , Female , Humans , Lupus Nephritis/blood , Lupus Nephritis/physiopathology , Lupus Nephritis/urine , Male , Middle Aged , ROC Curve , Renal Insufficiency/blood , Renal Insufficiency/etiology , Renal Insufficiency/urine , Young AdultABSTRACT
AIM: Various studies have reported that urinary neutrophil gelatinase-associated lipocalin (NGAL), an indicator of tubular damage, may be an effective biomarker of renal impairment in patients with diabetes. This study aimed to compare the ability of urinary alpha-1-microglobulin (a traditional tubular damage marker) with NGAL for evaluating renal insufficiency in patients with type-2 diabetes. METHODS: Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to determine whether 513 participants with type-2 diabetes had renal dysfunction. Urinary alpha-1-microglobulin-to-creatinine ratio (A1MCR) and NGAL-to-creatinine ratio (NCR) were calculated. RESULTS: Although both A1MCR and NCR were significantly higher among participants with renal insufficiency than among participants without renal damage, the difference in A1MCR values between participants with and without renal insufficiency was relatively greater than the difference in NCR values, especially among the male subjects. The correlation of ACR or eGFR with A1MCR was stronger than that of ACR or eGFR with NCR. A1MCR showed a good capability for detecting renal dysfunction (area under the curve = 0.80), its cut-off value was 14.82 mg/g, corresponding to 71.4% sensitivity and 73.1% specificity. The diagnostic efficiency of A1MCR was significantly higher than that of NCR. CONCLUSION: The results indicated that the traditional tubular damage marker A1MCR was more significantly associated with renal insufficiency defined by ACR and/or eGFR and may have a higher diagnostic efficiency compared with the efficiency of NCR in patients with type-2 diabetes.
Subject(s)
Alpha-Globulins/urine , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/urine , Lipocalin-2/urine , Renal Insufficiency/urine , Adult , Aged , Biomarkers/urine , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Middle Aged , Renal Insufficiency/etiologyABSTRACT
OBJECTIVE: The objective of this study was to compare the predictive performances of a glomerular filtration rate (GFR) model with a physiologically based pharmacokinetic (PBPK) model to predict total or renal clearance or area under the curve of renally excreted drugs in subjects with varying degrees of renal impairment. METHODS: From the literature, 11 studies were randomly selected in which total or renal clearance or area under the curve of drugs in subjects with different degrees of renal impairment were predicted by PBPK models. In these published studies, drugs were given to subjects intravenously or orally. The PBPK model was generally a whole-body model whereas the GFR model was as follows: Predicted total clearance (CLT) = CLT in healthy subjects × (GFR in RI/GFR in H), Predicted AUC = AUC in healthy subjects × (GFR in H/GFR in RI), where H is the healthy subjects and RI is renal impairment. The predicted clearance or area under the curve values using PBPK and GFR models were compared with the observed (experimental pharmacokinetic) values. The acceptable prediction error was within the 0.5- to 2-fold or 0.5- to 1.5-fold prediction error. RESULTS: There were 33 drugs with a total number of 101 observations (area under the curve, total and renal clearance in subjects with mild, moderate, and severe renal impairment). From PBPK and GFR models, out of 101 observations, 94 (93.1%) and 96 (95.0%) observations were within the 0.5- to 2-fold prediction error, respectively. CONCLUSIONS: This study indicates that the predictive power of a simple GFR model is similar to a PBPK model for the prediction of clearance or area under the curve in subjects with renal impairment. The GFR method is simple, robust, and reliable and can replace complex empirical PBPK models.
Subject(s)
Kidney/metabolism , Pharmaceutical Preparations/urine , Renal Elimination , Renal Insufficiency/metabolism , Renal Insufficiency/urine , Area Under Curve , Computer Simulation , Glomerular Filtration Rate , Humans , Kidney/drug effects , Metabolic Clearance Rate/physiology , Models, Biological , PharmacokineticsABSTRACT
OBJECTIVE: Most of the kidney dysfunction in HIV-positive children receiving antiretroviral therapy (ART) is attributed to tenofovir. There is a paucity of data on kidney dysfunction in tenofovir-naive children. The primary objective was to know the point prevalence of albuminuria and ß2-microglobulinuria in HIV-infected children aged 3-18 years receiving ART. Albuminuria and ß2-microglobulinuria were used as surrogates for glomerular and tubular dysfunction, respectively. The secondary objective was to determine their predictors. DESIGN: Cross-sectional study-design. METHODS: One hundred consecutive HIV-positive children (3-18 years) on ART were included. Spot urine sample was analyzed for urinary creatinine, total protein, microalbumin, and ß2-microglobulin. Albuminuria was defined as albumin to creatinine ratio of >30 mg/g; proteinuria as urine dipstick ≥trace or spot urine protein to creatinine ratio (uPCR) of ≥0.2. ß2-microglobulinuria was defined as ß2-microglobulin levels of >350 µg/L. RESULTS: There were 71 boys and 29 girls. Most of the children had WHO clinical stage I and were getting zidovudine-based regimen. Only 7 children were getting tenofovir. estimated Glomerular Filtration Rate and serum creatinine were normal in all children. Approximately half (48%) had renal dysfunction in the form of glomerular dysfunction (26%), tubular dysfunction (27%), or both (5%). Age at diagnosis was significantly associated with ß2-microglobulinuria (P = 0.044). None of the selected variables were associated with albuminuria. CONCLUSIONS: HIV-associated glomerular and tubular dysfunction is common in children receiving ART other than tenofovir. The standard guidelines should consider including routine urinary biomarker monitoring in children on ART.
Subject(s)
HIV Infections/complications , HIV Infections/drug therapy , HIV-1 , Renal Insufficiency/etiology , Adolescent , Albuminuria , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Proteinuria , Renal Insufficiency/urineABSTRACT
BACKGROUND: Excess cadmium (Cd) intake poses a general risk to health and to the kidneys in particular. Among indices of renal dysfunction under Cd burden measures are the urinary N-acetyl-ß-D-glucosidase (UNAG) and urinary ß2-microglobulin (Uß2-MG) enzymes. However, the end-pointed values and the Cd burden threshold remain controversial because the scopes fluctuate widely. METHODS: To ascertain the clinical benchmark dose of urinary Cd (UCd) burden for renal dysfunction, 1595 residents near a Cd site were surveyed. Urine was sampled and assayed. A benchmark dose low (BMDL) was obtained by fitting UCd levels and index levels. RESULTS: We found that over 50% of the subjects were suffering from Cd exposure as their UCd levels far exceeded the national standard threshold of 5.000 µg/g creatinine (cr). Further analysis indicated that Uß2-MG was more sensitive than UNAG for renal dysfunction. The BMDL for UCd was estimated as 3.486 U/g cr (male, where U is unit of enzyme) and 2.998 U/g cr (female) for UNAG. The BMDL for Uß2-MG, which is released into urine from glomerulus after Cd exposure, was found to be 2.506 µg/g cr (male, where µg is the unit of microglobulin) and 2.236 µg/g cr (female). CONCLUSIONS: Uß2-MG is recommended as the sensitivity index for renal dysfunction, with 2.2 µg/g cr as the threshold for clinical diagnosis. Our findings suggest that Uß2-MG is the better biomarker for exposure to Cd.
Subject(s)
Acetylglucosaminidase/urine , Cadmium/urine , Renal Insufficiency/diagnosis , beta 2-Microglobulin/urine , Aged , Biomarkers/urine , Cadmium/adverse effects , Environmental Exposure/adverse effects , Female , Humans , Male , Middle Aged , Renal Insufficiency/chemically induced , Renal Insufficiency/urineABSTRACT
Two studies evaluated the effects of renal and hepatic impairment on pharmacokinetics and safety of rivipansel (NCT02813798, NCT02871570). A single intravenous 840-mg rivipansel dose was administered to subjects with renal impairment or normal renal function in study 1005 and subjects with moderate hepatic impairment or normal hepatic function in study 1006. Plasma (both studies) and urine (study 1005) samples were collected for 96 hours postdose. All subjects in studies 1005 (n = 28) and 1006 (n = 16) completed all study procedures. Rivipansel exposure (AUCinf ) was 47%, 124%, and 437% higher and total clearance 30%, 57%, and 82% lower in the mild, moderate, and severe renal impairment groups, respectively, than in the normal renal function group. Overall rivipansel exposure was 20% lower and total clearance 31% higher in the moderate hepatic impairment group than in the normal hepatic function group. Ten treatment-emergent adverse events occurred in studies 1005 and 1006; no event was considered treatment related. As expected, clearance of rivipansel decreased with increasing renal impairment. The difference observed between rivipansel pharmacokinetics in subjects with moderate hepatic impairment and subjects with normal hepatic function was not considered clinically significant. Single doses of rivipansel were well tolerated in subjects with either renal or hepatic impairment.
Subject(s)
E-Selectin/antagonists & inhibitors , Glycolipids/pharmacokinetics , L-Selectin/antagonists & inhibitors , Liver Diseases/metabolism , P-Selectin/antagonists & inhibitors , Renal Insufficiency/metabolism , Administration, Intravenous , Adult , Aged , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/drug therapy , Area Under Curve , Case-Control Studies , Drug Tolerance , Female , Glycolipids/administration & dosage , Glycolipids/adverse effects , Humans , Liver Diseases/blood , Liver Diseases/urine , Male , Middle Aged , Non-Randomized Controlled Trials as Topic/methods , Renal Insufficiency/blood , Renal Insufficiency/urine , Safety , SelectinsABSTRACT
BACKGROUND: There is an increasing burden of non-communicable disease globally. Tenofovir disoproxil fumarate (TDF) is the most commonly prescribed antiretroviral drug globally. Studies show that patients receiving TDF are more prone to renal dysfunction at some point in time during treatment. Evaluation of kidney function is not routinely done in most HIV public clinics. Identification of renal dysfunction is key in resource constrained settings because managing patients with end stage renal disease is costly. METHOD: This was a cross-sectional study conducted at an outpatient clinic in 2018 involving patients on TDF for at least 6 months who were 18 years or older. Patients with documented kidney disease and pregnancy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula. Renal dysfunction was defined as any of the following; either eGFR< 60 mL/min/1.73m2,or proteinuria of ≥2+ on urine dipstick, glycosuria with normal blood glucose. Electrolyte abnormalities were also documented. RESULTS: We enrolled 278 participants. One hundred sixty nine (60.8%) were females, majority 234(84.2%) were < 50 years old, 205 (73.74%) were in WHO stage 1, most participants 271(97.5%) in addition to TDF were receiving lamivudine/efavirenz. The median age was 37(IQR 29-45) years; median duration on ART was 36 (IQR 24-60) months. The prevalence of renal dysfunction was 2.52% (7/278). Most noted electrolyte abnormality was hypocalcaemia (15.44%). CONCLUSIONS: The prevalence of renal dysfunction was low though some participants had hypocalcaemia. Screening for kidney disease should be done in symptomatic HIV infected patients on TDF.
Subject(s)
Anti-HIV Agents/therapeutic use , Glomerular Filtration Rate , Glycosuria/epidemiology , HIV Infections/drug therapy , Proteinuria/epidemiology , Renal Insufficiency/epidemiology , Tenofovir/therapeutic use , Adult , Alkynes/therapeutic use , Benzoxazines/therapeutic use , Cross-Sectional Studies , Cyclopropanes/therapeutic use , Drug Therapy, Combination , Female , Humans , Hypercalcemia/epidemiology , Hyperkalemia/epidemiology , Hyperphosphatemia/epidemiology , Hypocalcemia/epidemiology , Hypokalemia/epidemiology , Hypophosphatemia/epidemiology , Lamivudine/therapeutic use , Male , Middle Aged , Prevalence , Renal Insufficiency/urine , Uganda/epidemiologyABSTRACT
BACKGROUND: Acute kidney disease (AKD) describes acute or subacute damage and/or loss of kidney function for a duration of between 7 and 90 days after exposure to an acute kidney injury (AKI) initiating event. This study investigated the predictive ability of AKI biomarkers in predicting AKD in coronary care unit (CCU) patients. METHODS: A total of 269 (mean age: 64 years; 202 (75%) men and 67 (25%) women) patients admitted to the CCU of a tertiary care teaching hospital from November 2009 to September 2014 were enrolled. Information considered necessary to evaluate 31 demographic, clinical and laboratory variables (including AKI biomarkers) was prospectively recorded on the first day of CCU admission for post hoc analysis as predictors of AKD. Blood and urinary samples of the enrolled patients were tested for neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and interleukin-18 (IL-18). RESULTS: The overall hospital mortality rate was 4.8%. Of the 269 patients, 128 (47.6%) had AKD. Multivariate logistic regression analysis revealed that age, hemoglobin, ejection fraction and serum IL-18 were independent predictors of AKD. Cumulative survival rates at 5 years of follow-up after hospital discharge differed significantly (p < 0.001) between subgroups of patients diagnosed with AKD (stage 0A, 0C, 1, 2 and 3). The overall 5-year survival rate was 81.8% (220/269). Multivariate Cox proportional hazard analysis revealed that urine NGAL, body weight and hemoglobin level were independent risk factors for 5-year mortality. CONCLUSIONS: This investigation confirmed that AKI biomarkers can predict AKD in CCU patients. Age, hemoglobin, ejection fraction and serum IL-18 were independently associated with developing AKD in the CCU patients, and urine NGAL, body weight and hemoglobin level could predict 5-year survival in these patients.
Subject(s)
Acute Kidney Injury/blood , Acute Kidney Injury/urine , Renal Insufficiency/blood , Renal Insufficiency/urine , Acute Disease , Acute Kidney Injury/complications , Acute Kidney Injury/mortality , Age Factors , Aged , Biomarkers/blood , Biomarkers/urine , Body Weight , Clofibrate/blood , Clofibrate/urine , Coronary Care Units , Cystatin C/blood , Cystatin C/urine , Drug Combinations , Female , Follow-Up Studies , Hemoglobins/metabolism , Hospital Mortality , Humans , Interleukin-18/blood , Interleukin-18/urine , Male , Middle Aged , Phosphatidylcholines/blood , Phosphatidylcholines/urine , Proportional Hazards Models , Renal Insufficiency/etiology , Renal Insufficiency/mortality , Stroke Volume , Survival RateABSTRACT
BACKGROUND: Several studies have indicated that high albuminuria is associated with renal function decline. However, the relationship between the urinary albumin-to-creatinine ratio (ACR) and risk of developing tubular injury remains unclear. Our aim was to investigate the association of ACR with the risk of developing tubular impairment in patients with type 2 diabetes. METHODS: This longitudinal observational study compared baseline with follow-up data in 183 patients with type 2 diabetes. ACR, urinary alpha-1-microglobulin-to-creatinine ratio (A1MCR) and estimated glomerular filtration rate (eGFR) were used to evaluate albuminuira, tubular injury and glomerular filtration function, respectively. RESULTS: Levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and A1MCR were significantly different at the two-year follow-up compared with baseline levels. Among patients both with baseline ACR above and below 30 mg/g, the percentage with A1MCR > 15 mg/g clearly increased after follow-up (P < 0.05). The risk of A1MCR rising from normal ranges to >15 mg/g over the follow-up increased with increasing baseline ACR values lower baseline eGFR. Among the patients with baseline ACR > 63.10 mg/g, all showed increased A1MCR values at follow-up compared with baseline. In the multivariate regression analysis, the patients with baseline ACR > 63.10 mg/g had a strong risk of A1MCR rising from normal to >15 mg/g (odds ratio (OR) = 11.12, P = 0.001) over the follow-up, while the males had a 2.89-fold risk of A1MCR increasing from normal to >15 mg/g compared with females. CONCLUSION: Baseline ACR level is related to increased risk of developing renal tubular injury; in particular, this association is much stronger in patients with type 2 diabetes and baseline ACR > 63.10 mg/g.
Subject(s)
Albuminuria/urine , Creatinine/urine , Diabetes Mellitus, Type 2/complications , Kidney Function Tests/methods , Renal Insufficiency/diagnosis , Renal Insufficiency/urine , Female , Humans , Longitudinal Studies , Male , Middle Aged , Risk FactorsABSTRACT
BACKGROUND: Raccoon eyes or periorbital ecchymosis is caused by blood tracking into periorbital tissues, which is mostly recognized in injuries of head and neck, basal skull fractures, convexity fractures and facial fractures. It was also reported in systematic disorders, such as multiple myeloma, amyloidosis, Kaposi's sarcoma, migraine and neuroblastoma. However, it is unusual to see a patient showing periorbital purpura after kidney biopsy with no other ecchymosis. Here, we firstly reported this rare symptom after kidney biopsy in a patient who was finally diagnosed as immunoglobulin light chain (AL) amyloidosis. CASE PRESENTATION: A 64-year old woman was admitted to our clinic with 1.5 years history of sub-nephrotic proteinuria and slowly progressive deterioration of renal function. Laboratory -investigations revealed an M-peak in the λ fraction of IgA and concentrations of serum free-light-chain (FLC) were 44.95 mg/L for κ isotype and 173 mg/L for λ isotype. Unexpectedly the patient showed periorbital purpura 24 h later after kidney biopsy with no more other ecchymosis. Renal biopsy showed massively glomerulosclerosis, interstitial fibrosis with positively Congo red staining in mesangial areas. For fluorescent staining, the kidney tissue showed strongly λ light-chain deposition. The fibrils (8-12 nm in diameter) were confirmed by electron micrograph. CONCLUSIONS: This case firstly reported this rare symptom after the kidney biopsy in a patient who was finally diagnosed as AL amyloidosis. And this unique sign of periorbital ecchymosis warrants more attention as an early cue of amyloidosis.
Subject(s)
Biopsy/adverse effects , Ecchymosis , Eye Diseases , Immunoglobulin Light-chain Amyloidosis , Kidney/pathology , Renal Insufficiency , Biopsy/methods , Diagnosis, Differential , Disease Progression , Ecchymosis/diagnosis , Ecchymosis/etiology , Eye Diseases/diagnosis , Eye Diseases/etiology , Female , Humans , Immunoglobulin Light-chain Amyloidosis/complications , Immunoglobulin Light-chain Amyloidosis/pathology , Immunoglobulin Light-chain Amyloidosis/physiopathology , Immunoglobulin lambda-Chains/blood , Microscopy, Fluorescence/methods , Middle Aged , Renal Insufficiency/blood , Renal Insufficiency/etiology , Renal Insufficiency/physiopathology , Renal Insufficiency/urineABSTRACT
Consumption of either monosodium glutamate (MSG) or high-fat and high-fructose (HFF) diets changes the gut microbiome and hence contributes to development of several diseases. In this study, with an emphasis on kidney injury, hamsters were divided into 4 groups as follows: (1) hamsters fed with standard diet (control); (2) hamsters fed with standard diet and MSG in drinking water (MSG); (3) hamsters fed with high-fat and high-fructose diets (HFF), and (4) animals fed MSG+HFF. After 8 months, the animals were used for the study. Despite showing normal kidney function, hamsters fed with MSG+HFF exhibited signs of kidney damage as demonstrated by the highest expression levels of high-mobility group box-1 and kidney injury molecule-1 in kidney tissues, while slight changes of histopathological features in H&E-stained sections and normal levels of creatinine were observed, indicating possible early stages of kidney injury. Sequencing of the microbial 16S rRNA gene revealed that animals fed with the MSG+HFF diet had a higher ratio of gut Firmicutes/Bacteroidetes along with marked changes in abundance and diversity of gut microbiome compared to hamsters fed with MSG or HFF alone. In addition, 1H Nuclear magnetic resonance spectroscopy showed an elevation of urine p-cresol sulfate levels in the MSG+HFF group. These results indicate that consumption of both MSG and HFF increases the risk of kidney injury, induces gut dysbiosis and an increase in the amount of p-cresol sulfate in hamsters.
Subject(s)
Diet, Carbohydrate Loading/adverse effects , Diet, High-Fat/adverse effects , Dysbiosis/etiology , Fructose/administration & dosage , Gastrointestinal Microbiome/drug effects , Renal Insufficiency/etiology , Sodium Glutamate/pharmacology , Animals , Bacteroidetes/genetics , Cresols/urine , Cricetinae , Firmicutes/genetics , HMGB1 Protein/metabolism , Hepatitis A Virus Cellular Receptor 1/metabolism , Kidney/drug effects , Kidney/metabolism , Male , Mesocricetus , RNA, Ribosomal, 16S , Renal Insufficiency/urine , Sulfuric Acid Esters/urineABSTRACT
PURPOSE: In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. MATERIALS AND METHODS: Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. RESULTS: The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group. CONCLUSIONS: According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.
Subject(s)
Acetates/administration & dosage , Antioxidants/administration & dosage , Cyclopropanes/administration & dosage , Gamma Rays/adverse effects , Leukotriene Antagonists/administration & dosage , Quinolines/administration & dosage , Radiation-Protective Agents/administration & dosage , Renal Insufficiency/drug therapy , Renal Insufficiency/etiology , Sulfides/administration & dosage , Animals , Creatinine/blood , Creatinine/urine , Glutathione/analysis , Glutathione/metabolism , Kidney/metabolism , Male , Malondialdehyde/analysis , Malondialdehyde/metabolism , Mice , Mice, Inbred BALB C , Radiotherapy/adverse effects , Receptors, Leukotriene , Renal Insufficiency/blood , Renal Insufficiency/urineABSTRACT
Oxidative stress induced by long-term cyclosporine A (CsA) administration is a major cause of chronic nephrotoxicity, which is characterized by tubular atrophy, tubular cell apoptosis, and interstitial fibrosis in the progression of organ transplantation. Although hydrogen-rich water (HRW) has been used to prevent various oxidative stress-related diseases, its underlying mechanisms remain unclear. This study investigated the effects of HRW on CsA-induced nephrotoxicity and its potential mechanisms. After administration of CsA (25 mg/kg/day), rats were treated with or without HRW (12 mL/kg) for 4 weeks. Renal function and vascular activity were investigated. Histological changes in kidney tissues were analyzed using Masson's trichrome and terminal deoxynucleotidyl transferase dUTP nick-end labeling stains. Oxidative stress markers and the activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were also measured. We found that CsA increased the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), but it reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Such alterations induced vascular dysfunction, tubular atrophy, interstitial fibrosis, and tubular apoptosis. This was evident secondary to an increase in urinary protein, serum creatinine, and blood urea nitrogen, ultimately leading to renal dysfunction. Conversely, HRW decreased levels of ROS and MDA while increasing the activity of GSH and SOD. This was accompanied by an improvement in vascular and renal function. Moreover, HRW significantly decreased the level of Keap1 and increased the expression of Nrf2, NADPH dehydrogenase quinone 1, and heme oxygenase 1. In conclusion, HRW restored the balance of redox status, suppressed oxidative stress damage, and improved kidney function induced by CsA via activation of the Keap1/Nrf2 signaling pathway.
Subject(s)
Cyclosporine/adverse effects , Hydrogen/pharmacology , Immunosuppressive Agents/adverse effects , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Protective Agents/pharmacology , Renal Insufficiency/chemically induced , Signal Transduction/drug effects , Water/pharmacology , Animals , Apoptosis/drug effects , Blood Urea Nitrogen , Creatinine/blood , Creatinine/urine , Male , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Renal Insufficiency/urine , Superoxide Dismutase/metabolism , Water/chemistryABSTRACT
CC-122 (Avadomide) is a nonphthalimide analogue of thalidomide that has multiple pharmacological activities including immune modulation of several immune cell subsets, antigrowth activity, antiproliferative activity, and antiangiogenic activity. CC-122 as monotherapy and in combination with other agents is being evaluated for multiple indications including hematologic malignancies and advanced solid tumors. Given that renal clearance is one of the major routes of elimination for CC-122 and its clearance/exposure could be affected by renal impairment, a total of 50 subjects with various degrees of renal function were enrolled in an open-label, single-dose study to evaluate the impact of renal impairment on CC-122 pharmacokinetic disposition. The study showed that following administration of a single oral dose of 3 mg CC-122, renal impairment reduced both the apparent total plasma clearance and renal clearance of CC-122, but it had less impact on CC-122 absorption, as demonstrated by similar Tmax and Cmax among groups with various degrees of renal function. Compared with exposure in subjects with normal renal function, total plasma exposure to CC-122 increased by â¼20%, â¼50%, and â¼120% in subjects with mild, moderate, and severe renal insufficiency, respectively. Results from this study combined with modeling/simulation suggest that dose adjustments are necessary in patients with moderate or severe but not with mild renal impairment. Finally, a single dose of 3 mg CC-122 was safe and well tolerated by healthy subjects and subjects with mild, moderate, and severe renal impairment.
Subject(s)
Genetic Pleiotropy/drug effects , Hematologic Neoplasms/drug therapy , Piperidones/pharmacokinetics , Quinazolinones/pharmacokinetics , Renal Insufficiency/blood , Adaptor Proteins, Signal Transducing/drug effects , Adaptor Proteins, Signal Transducing/metabolism , Adult , Aged , Carcinoma, Hepatocellular/drug therapy , Case-Control Studies , Cytochrome P-450 CYP1A2 Inhibitors/administration & dosage , Cytochrome P-450 CYP1A2 Inhibitors/adverse effects , Cytochrome P-450 CYP1A2 Inhibitors/pharmacokinetics , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Cytochrome P-450 CYP3A Inhibitors/pharmacokinetics , Dose-Response Relationship, Drug , Drug Interactions , Female , Genetic Pleiotropy/genetics , Glioblastoma/drug therapy , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Piperidones/administration & dosage , Piperidones/adverse effects , Piperidones/pharmacology , Quinazolinones/administration & dosage , Quinazolinones/adverse effects , Quinazolinones/pharmacology , Renal Insufficiency/ethnology , Renal Insufficiency/metabolism , Renal Insufficiency/urine , Safety , Severity of Illness Index , Ubiquitin-Protein Ligases/drug effects , Ubiquitin-Protein Ligases/metabolismABSTRACT
BACKGROUND: Preventing progression to end-stage renal disease (ESRD) in advanced IgA nephropathy (IgAN) patients with impaired renal function remains challenging. We analyzed the efficacy of tonsillectomy combined with steroid pulse therapy (TSP). METHODS: In this retrospective analysis, IgAN patients with proteinuria > 0.5 g/day and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were divided into three groups: patients treated with TSP (TSP group; n = 23), oral prednisolone (oPSL group; n = 41), and conservative therapy (CONS group, n = 51). We analyzed the clinical and histological backgrounds, remission of urinary findings, and renal survival rate to a 25% decline in eGFR from baseline, and incidence of ESRD. RESULTS: There were significant differences in the patients' backgrounds among the groups. Therefore, we adjusted the background using propensity score marching between TSP group and oPSL or CONS group. The 5-year remission rate of hematuria was significantly higher in the TSP group than in the oPSL group, and that of both hematuria and proteinuria was significantly higher in the TSP group than in the CONS group. The 10-year renal survival rate was significantly higher in the TSP group than in the oPSL and CONS groups. In a multivariate Cox regression analysis, TSP was found to be an independent factor for the 25% decline in eGFR in entire cohort. The adverse effect frequency in the TSP group was similar to the CONS group. CONCLUSIONS: TSP can effectively induce remission of urinary abnormality and improve the prognosis without frequent adverse effects in IgAN patients with impaired renal function.
Subject(s)
Glomerulonephritis, IGA/drug therapy , Glucocorticoids/administration & dosage , Methylprednisolone/administration & dosage , Renal Insufficiency/drug therapy , Tonsillectomy , Adult , Combined Modality Therapy , Female , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/surgery , Glomerulonephritis, IGA/urine , Humans , Male , Middle Aged , Prognosis , Remission Induction , Renal Insufficiency/immunology , Renal Insufficiency/surgery , Renal Insufficiency/urine , Retrospective Studies , Tissue SurvivalABSTRACT
AIMS/INTRODUCTION: To clarify the prevalence of albuminuria and renal dysfunction, and related factors in Japanese patients with diabetes, we analyzed the baseline data of the Japan Diabetes Complication and its Prevention prospective study. MATERIALS AND METHODS: We used the data of 355 patients with type 1 diabetes and 5,194 patients with type 2 diabetes to evaluate the prevalence of albuminuria and renal dysfunction, and related factors. A binomial logistic regression analysis was used to investigate independent contributing factors for estimated glomerular filtration rate <60 mL/min/1.73 m2 or albuminuria. RESULTS: The prevalence of microalbuminuria and macroalbuminuria was 15.2% (54/355) and 3.1% (11/355) in type 1 diabetes patients, and 25.0% (1,298/5,194) and 5.1% (265/5,194) in type 2 diabetes patients, respectively. The proportion of renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) was 9.9% (35/355) in type 1 diabetes patients, and 15.3% (797/5,194) in type 2 diabetes patients. The proportion of patients with renal dysfunction with normoalbuminuria was 7.3% (26/355) for type 1 diabetes patients, and 9.0% (467/5,194) for type 2 diabetes patients. The factors related to albuminuria in type 2 diabetes patients were glycated hemoglobin, hypertension, age, duration of diabetes, body mass index and estimated glomerular filtration rate. In contrast, factors to related renal dysfunction were age, duration of diabetes, dyslipidemia, hypertension, body mass index, male sex and albuminuria. CONCLUSIONS: We showed the recent prevalence of albuminuria and renal dysfunction, and related factors in Japanese type 1 and type 2 diabetes patients using the baseline data of the Japan Diabetes Complication and its Prevention prospective study. The current results suggest that renal disease in patients with type 2 diabetes is heterogeneous, and different mechanisms might be involved in albuminuria and deterioration of renal function.