Subject(s)
Atypical Hemolytic Uremic Syndrome/complications , Glomerulonephritis, IGA/etiology , Pregnancy Complications , Renal Insufficiency/etiology , Adolescent , Atypical Hemolytic Uremic Syndrome/diagnosis , Atypical Hemolytic Uremic Syndrome/genetics , Atypical Hemolytic Uremic Syndrome/therapy , Biopsy , DNA Mutational Analysis , Female , Fluorescent Antibody Technique , Genetic Predisposition to Disease , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/therapy , Humans , Kidney Transplantation , Mutation, Missense , Phenotype , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/genetics , Pregnancy Complications/therapy , Renal Dialysis , Renal Insufficiency/diagnosis , Renal Insufficiency/therapy , Thrombomodulin/genetics , Treatment OutcomeABSTRACT
OBJECTIVE: Increasing evidence links TGF-ß1 to progression of renal fibrosis including its association with diabetic nephropathy (DN). Current ELISA assays are not sensitive enough to measure TGF-ß1 in the urine of many clinically healthy individuals, even those with established renal disease. The objective of this study was to validate a sensitive urinary assay for TGF-ß1 and compare levels between healthy controls and patients with established DN. DESIGN AND METHODS: An ELISA method (R&D Systems) was utilized together with an amplification step to assay TGF-ß1 in urine samples from 190 patients with DN and 80 healthy controls. RESULTS: Using an ELAST (Perkin Elmer, Inc) amplification step, the ELISA for urinary TGF-ß1 had a limit of quantification of 15.6 pg/mL and limit of detection of 7 pg/mL. Preliminary studies demonstrated that TGF-ß1 was stable if urine was frozen promptly at -70°C without preservatives. Using this assay, 22/80 controls (27%) had detectable levels of urinary TGF-ß1 (range <7 to 40.9 pg/mL; mean±SD 6.4±11.1 pg/mL). This was significantly lower (p<0.0001) than in the DN group in whom 114/190 (60%) had detectable levels of urinary TGF-ß1 (range <7 to 526.4 pg/mL; mean±SD 20.4±45.8 pg/mL). Urinary protein and TGF-ß1 concentrations demonstrated modest correlation in patients with DN (r=0.47, P<0.001). TGF-ß1 measurement in patients with DN did not demonstrate significant association with progression of proteinuria or increase in serum creatinine during the next 12 months of follow-up. CONCLUSION: We have validated a sensitive ELISA assay for urinary TGF-ß1, and demonstrated correlations with the degree of proteinuria and higher levels in patients with DN compared to controls. Additional study will be necessary in order to determine if serial testing can predict renal prognosis independent of known prognostic factors for patients with DN.
Subject(s)
Diabetes Mellitus/urine , Diabetic Nephropathies/urine , Enzyme-Linked Immunosorbent Assay/standards , Proteinuria/urine , Transforming Growth Factor beta1/urine , Aged , Case-Control Studies , Creatinine/blood , Diabetes Mellitus/blood , Diabetes Mellitus/physiopathology , Diabetic Nephropathies/blood , Diabetic Nephropathies/physiopathology , Female , Humans , Male , Middle Aged , Protein Stability , Proteinuria/blood , Proteinuria/physiopathology , Sensitivity and SpecificityABSTRACT
Acute kidney injury (AKI) is costly and is associated with increased mortality and morbidity. An understanding of the renal physiologic changes that occur during pregnancy is essential for proper evaluation, diagnosis, and management of AKI. As in the general population, AKI can occur from prerenal, intrinsic, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is the recommended therapeutic option, with additional therapies indicated for each specific disease entity. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management, prevention of adverse maternal outcomes, and safe delivery of the fetus. In pregnant women with pre-existing kidney disease, the degree of renal dysfunction is the major determining factor of pregnancy outcomes, which may further be complicated by a prior history of hypertension.
