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Saudi Journal of Kidney Diseases and... Mar 2023According to the current guidelines, renal biopsies are performed in systemic lupus erythematosus (SLE) patients for proteinuria of 0.5 g/24 h or higher. Renal pathology...
According to the current guidelines, renal biopsies are performed in systemic lupus erythematosus (SLE) patients for proteinuria of 0.5 g/24 h or higher. Renal pathology may be present in patients with lower-level proteinuria (<0.5 g/24 h). We aimed to review the renal histopathology in SLE patients, with lower levels of proteinuria. In this retrospective study, we retrieved SLE patients' data, including 24-h urinary protein excretion and renal histopathology results. We compared various parameters in different lupus nephritis (LN) classes and in different levels of proteinuria (urinary protein <0.5 g, 0.5 to <1 g, and ≥1 g per 24 h). Out of 476 patients, 274 (57.6%) had proteinuria of <0.5 g, 44 (9.2%) had 0.5 to <1 g, and 158 (33.2%) had ≥1 g per 24 h. SLE patients with proteinuria of <0.5 g/24 h were found to have LN, including the proliferative classes. Of the 299 LN cases confirmed by a renal biopsy, low-level proteinuria (<0.5 g) was found in 39.8% of all LN patients, in 50% of patients with Class III LN, 33.3% of those with Class IV LN, 31.4% of those with Class V LN, and 41.4% of those with other LN classes (II/V, III/V, and IV/V). Overall, 35.9% (87/242) of patients with the proliferative LN classes (III, IV, V, II/V, III/V and IV/V) had low-level proteinuria of <0.5 g/24 h. SLE patients with low-level proteinuria had significant renal pathology. Our study suggests there is a need to perform renal biopsies at lower levels of proteinuria.
Topics: Humans; Retrospective Studies; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Proteinuria
PubMed: 38146725
DOI: 10.4103/1319-2442.391894 -
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 -
Journal of Epidemiology Nov 2021
Topics: Cholelithiasis; Creatinine; Humans; Proteinuria
PubMed: 34421082
DOI: 10.2188/jea.JE20210281 -
Nefrologia 2021In nephrotic syndrome, increased podocyturia accompanies pathologic proteinuria. The therapeutic regimen with enalapril, losartan and amiloride could reduce both... (Comparative Study)
Comparative Study
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 to 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 39mg/m/h and mean proteinuria at the end was 24mg/m/h, while in group B 14 patients were treated and the initial average proteinuria was 36mg/m/h and the end average proteinuria was 13mg/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; Child; Child, Preschool; Drug Combinations; Drug Resistance; Enalapril; Female; Glucocorticoids; Humans; Losartan; Male; Nephrotic Syndrome; Proteinuria; Treatment Outcome
PubMed: 33722403
DOI: 10.1016/j.nefro.2020.11.014 -
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 -
Veterinary Journal (London, England :... Jun 2016Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with...
Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required.
Topics: Animals; Creatinine; Dog Diseases; Dogs; Female; Hypertriglyceridemia; Lipoprotein Lipase; Male; Minnesota; Ohio; Proteinuria; Species Specificity; Triglycerides
PubMed: 27256031
DOI: 10.1016/j.tvjl.2016.04.009 -
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 -
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 -
PloS One 2020Recent advances in neonatal care have improved the survival rate of those born premature. But prenatal conditions, premature birth and clinical interventions can lead to...
Recent advances in neonatal care have improved the survival rate of those born premature. But prenatal conditions, premature birth and clinical interventions can lead to transient and permanent problems in these fragile patients. Premature birth (<36 gestational weeks) occurs during critical renal development and maturation. Some consequences have been observed but the exact pathophysiology is still not entirely known. This experimental animal study aims to investigate the effect of premature birth on postnatal nephrogenesis in premature neonatal rabbits compared to term rabbits of the same corrected age. We analyzed renal morphology, glomerular maturity and functional parameters (proteinuria and protein/creatinine ratio) in three cohorts of rabbit pups: preterm (G28), preterm at day 7 of life (G28+7) and term at day 4 of life (G31+4). We found no significant differences in kidney volume and weight, and relative kidney volume between the cohorts. Nephrogenic zone width increased significantly over time when comparing G31 + 4 to G28. The renal corpuscle surface area, in the inner cortex and outer cortex, tended to decrease significantly after birth in both preterm and term groups. With regard to glomerular maturity, we found that the kidneys in the preterm cohorts were still in an immature state (presence of vesicles and capillary loop stage). Importantly, significant differences in proteinuria and protein/creatinine ratio were found. G28 + 7 showed increased proteinuria (p = 0.019) and an increased protein/creatinine ratio (p = 0.023) in comparison to G31 +4. In conclusion, these results suggest that the preterm rabbit kidney tends to linger in the immature glomerular stages and shows signs of a reduced renal functionality compared to the kidney born at term, which could in time lead to short- and long-term health consequences.
Topics: Animals; Animals, Newborn; Disease Models, Animal; Female; Kidney Glomerulus; Pregnancy; Premature Birth; Proteinuria; Rabbits; Survival Analysis
PubMed: 33166318
DOI: 10.1371/journal.pone.0241384