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The Journal of Clinical Endocrinology... Jan 2021Hypothyroidism is associated with reversible decline in kidney function as measured by estimated glomerular filtration rate (eGFR). eGFR and proteinuria are the most... (Observational Study)
Observational Study
CONTEXT
Hypothyroidism is associated with reversible decline in kidney function as measured by estimated glomerular filtration rate (eGFR). eGFR and proteinuria are the most important markers for clinical assessment of kidney function. Though hypothyroidism is associated with proteinuria in cross-sectional data, the impact of treatment on proteinuria is unknown.
OBJECTIVE
This study explores the effect of thyroid hormone replacement therapy on eGFR and 24-hour urine protein excretion in patients with severe primary hypothyroidism.
DESIGN AND PARTICIPANTS
This study was a prospective, observational cohort study in adults with severe primary hypothyroidism (serum thyrotropin [TSH] > 50 µIU/mL). Individuals with preexisting or past kidney disease, kidney or urinary tract abnormalities, calculi or surgery, diabetes mellitus, or hypertension were excluded. The participants received thyroid hormone replacement therapy. Thyroid functions, eGFR, 24-hour urine protein excretion, and biochemical parameters were measured at baseline and 3 months.
SETTING
This study took place at a single center, a tertiary care referral and teaching hospital.
RESULTS
Of 44 enrolled participants, 43 completed 3 months of follow-up. At 3 months, serum TSH levels decreased and thyroxine levels increased (P < .001 for both). Significant increases in eGFR (mean difference, 18.25 ± 19.49 mL/min/1.73 m2; 95% CI, 12.25 to 24.25, P < .001) and declines in 24-hour urine protein excretion (mean difference, -68.39 ± 125.89 mg/day; 95% CI, -107.14 to -29.65, P = .001) were observed. Serum cholesterol and low-density lipoprotein levels also significantly decreased (P < .001).
CONCLUSIONS
Thyroid hormone replacement therapy in patients with severe primary hypothyroidism improves eGFR and decreases 24-hour urine protein excretion, thereby suggesting reversible alterations.
Topics: Adult; Cohort Studies; Cross-Sectional Studies; Female; Follow-Up Studies; Glomerular Filtration Rate; Hormone Replacement Therapy; Humans; Hypothyroidism; India; Kidney; Male; Middle Aged; Prospective Studies; Proteinuria; Renal Insufficiency, Chronic; Severity of Illness Index; Thyroxine
PubMed: 33245744
DOI: 10.1210/clinem/dgaa871 -
British Journal of Pharmacology Jun 2022Preeclampsia, characterized by hypertension, proteinuria and restriction of fetal growth, is one of the leading causes of maternal and perinatal mortality. So far, there...
BACKGROUND AND PURPOSE
Preeclampsia, characterized by hypertension, proteinuria and restriction of fetal growth, is one of the leading causes of maternal and perinatal mortality. So far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of supplementation with l-citrulline in Dahl salt-sensitive rats, a model of superimposed preeclampsia.
EXPERIMENTAL APPROACH
Parental Dahl salt-sensitive rats were treated with l-citrulline (2.5 g·L in drinking water) from the day of mating to the end of lactation period. Blood pressure was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant Dahl salt-sensitive rats was assessed by wire myograph.
KEY RESULTS
In Dahl salt-sensitive rats, l-citrulline supplementation significantly reduced maternal blood pressure, proteinuria and levels of circulating soluble fms-like tyrosine kinase 1. l-Citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium-derived hyperpolarizing factor-mediated vasorelaxation in resistance arteries. l-Citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, l-citrulline down-regulated genes involved in the TLR4 and NF-κB signalling pathways.
CONCLUSION AND IMPLICATIONS
This study shows that l-citrulline supplementation reduced gestational hypertension and improved placentation and fetal growth in a rat model of superimposed preeclampsia. l-Citrulline supplementation may provide an effective and safe therapeutic strategy for preeclampsia that benefits both the mother and the fetus.
Topics: Animals; Biological Factors; Citrulline; Female; Humans; Male; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; Rats; Rats, Inbred Dahl
PubMed: 34935131
DOI: 10.1111/bph.15783 -
Journal of Epidemiology Nov 2021
Topics: Cholelithiasis; Creatinine; Humans; Proteinuria
PubMed: 34421082
DOI: 10.2188/jea.JE20210281 -
European Journal of Medical Research Mar 2023Podocyte injury is associated with IgA nephropathy (IgAN) prognosis. Mitochondrial dysfunction is a major contributor to podocyte injury and death. Mitofusin2 (Mfn2)...
BACKGROUND
Podocyte injury is associated with IgA nephropathy (IgAN) prognosis. Mitochondrial dysfunction is a major contributor to podocyte injury and death. Mitofusin2 (Mfn2) plays an important role in regulating the morphology and function of mitochondria. This study aimed to investigate the potential of Mfn2 as a biomarker to evaluate the degree of podocyte injury.
METHODS
This single-center, retrospective study enrolled 114 patients with biopsy-proven IgAN. Immunofluorescence and TUNEL staining were applied, and clinical and pathological features were compared between patients with different patterns of Mfn2 expression.
RESULTS
In IgAN, Mfn2 is mainly expressed in podocytes and significantly associated with nephrin, TUNEL, and Parkin staining. Among the 114 IgAN patients, 28 (24.56%) did not exhibit Mfn2 expression in podocytes. The patients in the Mfn2-negative group had lower serum albumin (34.43 ± 4.64 g/L vs. 36.48 ± 3 .52 g/L, P = 0.015) and estimated glomerular filtration rate (eGFR) (76.59 ± 35.38 mL/min vs. 92.13 ± 25.35 mL/min, P = 0.013), higher 24 h proteinuria (2.48 ± 2.72 g/d vs. 1.27 ± 1.31 g/d, P = 0.002), serum creatinine (Scr) (107.39 ± 57.97 μmol/L vs. 84.70 ± 34.95 μmol/L, P = 0.015), blood urea nitrogen (BUN) (7.36 ± 4.45 mmol/L vs. 5.68 ± 2.14 mmol/L, P = 0.008), and higher S/T scores (92.86% vs. 70.93% and 42.85% vs. 15.12%, respectively, P < 0.05). In the Mfn2-negative group, the mitochondria were punctate and round ridges disappeared, and a lower length-to-width ratio and much higher M/A ratio were observed. Correlation analysis showed that the intensity of Mfn2 was negatively correlated with Scr (r = - 0.232, P = 0.013), 24 h proteinuria (r = - 0.541, P = 0.001), and the degree of podocyte effacement (r = - 0.323, P = 0.001), and positively correlated with eGFR (r = 0.213, P = 0.025). Logistic regression analysis showed that the Mfn2-negative group had a higher risk of severe podocyte effacement (≥ 50%) (OR = 3.061, P = 0.019).
CONCLUSION
Mfn2 was negatively correlated with proteinuria and renal function. A lack of Mfn2 in podocytes indicates severe podocyte injury and a high degree of podocyte effacement.
Topics: Humans; Glomerular Filtration Rate; Glomerulonephritis, IGA; Podocytes; Proteinuria; Retrospective Studies; Mitochondrial Proteins; GTP Phosphohydrolases
PubMed: 36998021
DOI: 10.1186/s40001-023-01107-5 -
Journal of Veterinary Internal Medicine 2024Amyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in...
BACKGROUND
Amyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in shelter cats in Italy and was associated with azotemia and proteinuria.
OBJECTIVES
Investigate urine protein profiles and diagnostic biomarkers in cats with renal AA amyloidosis.
ANIMALS
Twenty-nine shelter cats.
METHODS
Case-control study. Cats with renal proteinuria that died or were euthanized between 2018 and 2021 with available necropsy kidney, liver and spleen samples, and with surplus urine collected within 30 days before death, were included. Histology was used to characterize renal damage and amyloid amount and distribution; immunohistochemistry was used to confirm AA amyloidosis. Urine protein-to-creatinine (UPC) and urine amyloid A-to-creatinine (UAAC) ratios were calculated, and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and liquid chromatography-mass spectrometry (LC-MS) of proteins were performed.
RESULTS
Twenty-nine cats were included. Nineteen had AA amyloidosis with renal involvement. Cats with AA amyloidosis had a higher UPC (median, 3.9; range, 0.6-12.7 vs 1.5; 0.6-3.1; P = .03) and UAAC ratios (median, 7.18 × 10 ; range, 23 × 10 -21.29 × 10 vs 1.26 × 10 ; 0.21 × 10 -6.33 × 10 ; P = .04) than unaffected cats. The SDS-AGE identified mixed-type proteinuria in 89.4% of cats with AA amyloidosis and in 55.6% without AA amyloidosis (P = .57). The LC-MS identified 63 potential biomarkers associated with AA amyloidosis (P < .05). Among these, urine apolipoprotein C-III was higher in cats with AA amyloidosis (median, 1.38 × 10 ; range, 1.85 × 10 -5.29 × 10 vs 1.76 × 10 ; 0.0 × 10 -1.38 × 10 ; P = .01). In the kidney, AA-amyloidosis was associated with glomerulosclerosis (P = .02) and interstitial fibrosis (P = .05).
CONCLUSIONS AND CLINICAL IMPORTANCE
Renal AA amyloidosis is associated with kidney lesions, increased proteinuria and increased urine excretion of SAA in shelter cats. Additional studies are needed to characterize the role of lipid transport proteins in the urine of affected cats.
Topics: Cats; Animals; Creatinine; Case-Control Studies; Kidney; Amyloidosis; Proteinuria; Serum Amyloid A Protein; Cat Diseases
PubMed: 37991136
DOI: 10.1111/jvim.16920 -
British Journal of Cancer Feb 2022Hypertension and proteinuria are common bevacizumab-induced toxicities. No validated biomarkers are available for identifying patients at risk of these toxicities. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hypertension and proteinuria are common bevacizumab-induced toxicities. No validated biomarkers are available for identifying patients at risk of these toxicities.
METHODS
A genome-wide association study (GWAS) meta-analysis was performed in 1039 bevacizumab-treated patients of European ancestry in four clinical trials (CALGB 40502, 40503, 80303, 90401). Grade ≥2 hypertension and proteinuria were recorded (CTCAE v.3.0). Single-nucleotide polymorphism (SNP)-toxicity associations were determined using a cause-specific Cox model adjusting for age and sex.
RESULTS
The most significant SNP associated with hypertension with concordant effect in three out of the four studies (p-value <0.05 for each study) was rs6770663 (A > G) in KCNAB1, with the G allele increasing the risk of hypertension (p-value = 4.16 × 10). The effect of the G allele was replicated in ECOG-ACRIN E5103 in 582 patients (p-value = 0.005). The meta-analysis of all five studies for rs6770663 led to p-value = 7.73 × 10, close to genome-wide significance. The most significant SNP associated with proteinuria was rs339947 (C > A, between DNAH5 and TRIO), with the A allele increasing the risk of proteinuria (p-value = 1.58 × 10).
CONCLUSIONS
The results from the largest study of bevacizumab toxicity provide new markers of drug safety for further evaluations. SNP in KCNAB1 validated in an independent dataset provides evidence toward its clinical applicability to predict bevacizumab-induced hypertension. ClinicalTrials.gov Identifier: NCT00785291 (CALGB 40502); NCT00601900 (CALGB 40503); NCT00088894 (CALGB 80303) and NCT00110214 (CALGB 90401).
Topics: Aged; Angiogenesis Inhibitors; Bevacizumab; Female; Genome-Wide Association Study; Humans; Hypertension; Kv1.3 Potassium Channel; Male; Middle Aged; Neoplasms; Polymorphism, Single Nucleotide; Proteinuria
PubMed: 34616010
DOI: 10.1038/s41416-021-01557-w -
Journal of the American Society of... Feb 2021On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a...
BACKGROUND
On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown.
METHODS
In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to <1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR).
RESULTS
During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups.
CONCLUSIONS
Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints.
Topics: Adult; Disease Progression; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Kidney Failure, Chronic; Male; Middle Aged; Outcome Assessment, Health Care; Proportional Hazards Models; Proteinuria; Remission Induction; Retrospective Studies; Time Factors
PubMed: 33514642
DOI: 10.1681/ASN.2020030349 -
Nutrients Sep 2022The objective of this study was to examine whether a higher number of ideal cardiovascular health (CVH) metrics are beneficial for lowering the risk of proteinuria. This...
The objective of this study was to examine whether a higher number of ideal cardiovascular health (CVH) metrics are beneficial for lowering the risk of proteinuria. This is a retrospective cohort study with an average follow-up of 5 years. Participants between 21 and 75 years old and without a history of cardiovascular disease and proteinuria were enrolled. CVH metrics, including smoking, diet, physical activity, blood pressure, body mass index (BMI), cholesterol, and fasting glucose, were assessed by questionnaires, physical examination, and blood analysis. Proteinuria was assessed by dipstick measurement. During the follow-up period, 169,366 participants were enrolled, and 1481 subjects developed proteinuria. A higher number of ideal CVH metrics was related to a lower risk of proteinuria after adjustment. Among the components of CVH metrics, ideal blood pressure (HR = 0.33, 95% CI = 0.25-0.43), fasting glucose (HR = 0.17, 95% CI = 0.12-0.22), and BMI (HR = 0.20, 95% CI = 0.15-0.27) had beneficial effects on proteinuria. Despite no significant benefit of diet score, the corresponding lower sodium intake showed a lower risk of proteinuria (HR = 0.58, 95% CI = 0.43-0.79). Incident proteinuria was inversely related to the number of ideal CVH metrics. CVH metrics may be a predictor of proteinuria, and achieving a higher number of ideal scores should be recommended as a proteinuria prevention strategy.
Topics: Adult; Aged; Blood Pressure; Cardiovascular Diseases; Cholesterol; Cross-Sectional Studies; Glucose; Health Status; Humans; Middle Aged; Proteinuria; Retrospective Studies; Risk Factors; Sodium, Dietary; Young Adult
PubMed: 36235692
DOI: 10.3390/nu14194040 -
Nefrologia 2021In nephrotic syndrome, increased podocyturia accompanies pathologic proteinuria. The therapeutic regimen with enalapril, losartan and amiloride could reduce both...
INTRODUCCION
In nephrotic syndrome, increased podocyturia accompanies pathologic proteinuria. The therapeutic regimen with enalapril, losartan and amiloride could reduce both variables.
OBJETIVES
Evaluate the anti-proteinuric effect of 2 non-immunological therapeutic regimens, the quantitative relationship between podocyturia and proteinuria.
MATERIAL AND METHODS
We included children aged 4-12 years with corticoresistant nephrotic syndrome, using 2 different schemes: group A, enalapril + losartan, and group B, enalapril + losartan + amiloride.
RESULTS
In group A, 17 patients completed the study, the initial mean proteinuria was 39 mg/m/h and mean proteinuria at the end was 24 mg/m/h, while in group B 14 patients were treated and the initial average proteinuria was 36 mg/m/h and the end average proteinuria was 13 mg/m/h. The paired T test showed significant differences in the decrease in proteinuria, for patients in group B without variation in podocyturia. The 2 factors associated with an increase in proteinuria were podocyturia and the time elapsed from the diagnosis of cortico-resistant nephrotic syndrome to the start of treatment anti-proteinuric.
CONCLUSIONS
The use of amiloride decreased proteinuria, without significantly modifying podocyturia; we did not observe a positive relationship between both variables.
Topics: Amiloride; Angiotensin-Converting Enzyme Inhibitors; Child; Enalapril; Humans; Losartan; Nephrotic Syndrome; Proteinuria
PubMed: 36166246
DOI: 10.1016/j.nefroe.2021.08.005 -
Journal of the American Society of... Jul 2024
Topics: Proteinuria; Humans; Kidney Tubules; Kidney Glomerulus; Animals
PubMed: 38652545
DOI: 10.1681/ASN.0000000000000357