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Clinical and Experimental Nephrology Mar 2023Vaccines for coronavirus disease 2019 (COVID-19) have been developed and are recommended for patients with chronic kidney disease; however, it has been reported that...
BACKGROUND
Vaccines for coronavirus disease 2019 (COVID-19) have been developed and are recommended for patients with chronic kidney disease; however, it has been reported that glomerulonephritis worsens after vaccination. We aimed to elucidate the incidence and association between COVID-19 vaccination and glomerulonephritis relapse.
METHODS
We investigated the onset of renal events and adverse reactions after COVID-19 vaccination in 111 patients diagnosed with glomerulonephritis. Renal events were defined as worsening hematuria, increased proteinuria, and an increased creatine level over 1.5-fold from baseline.
RESULTS
Patients were 57 ± 18 years old (55.9% female) and had an estimated glomerular filtration rate of 57.0 ± 25.0 ml/min/1.73 m. A pathological diagnosis of IgA nephropathy was confirmed in 55.0%, minimal change disease in 22.5%, and membranous nephropathy in 10.8% of the patients. The BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines were administered in 88.2% and 11.7% of the cases, respectively. Renal events were observed in 22.5% of patients, 10.8% had increased proteinuria, 12.6% had worsening hematuria, and 1.8% received additional immunosuppressive treatment. Only 0.9% required temporary hemodialysis from exacerbation of renal dysfunction. Renal events were higher in younger patients (P = 0.02), being highest in those with IgA nephropathy, but there was no difference in the incidence between pathological diagnoses. There was a significantly higher incidence of renal events in patients with fever (P = 0.02).
CONCLUSIONS
COVID-19 vaccination and glomerulonephritis relapse may be related, but further research is needed.
Topics: Humans; Female; Adult; Middle Aged; Aged; Male; Glomerulonephritis, IGA; COVID-19 Vaccines; Hematuria; BNT162 Vaccine; COVID-19; Glomerulonephritis; Proteinuria; Chronic Disease; Vaccination
PubMed: 36422760
DOI: 10.1007/s10157-022-02299-6 -
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 -
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 -
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 -
European Journal of Obstetrics,... Jul 2022During normal pregnancy, blood volume increases by nearly two liters. Distinctively, the absence coupled with the extreme extent regarding the volume expansion, are... (Review)
Review
During normal pregnancy, blood volume increases by nearly two liters. Distinctively, the absence coupled with the extreme extent regarding the volume expansion, are likely accompanied with pathological conditions. Undoubtedly, preeclampsia, defined as the appearance of hypertension and organ deficiency, such as proteinuria during the second half of pregnancy, is not a homogenous disease. Clinically speaking, two main types of preeclampsia can be distinguished, in which a marked difference between them is vascular condition, and consequently, the blood volume. The "classic" preeclampsia, as a two-phase disease, described in the first, latent phase, in which, placenta development is diminished. Agents from this malperfused placenta generate a maternal disease, the second phase, in which endothelial damage leads to hypertension and organ damage due to vasoconstriction and thrombotic microangiopathy. In this hypovolemia-associated condition, decreasing platelet count, signs of hemolysis, renal and liver involvement are characteristic findings; proteinuria is marked and increasing. In the terminal phase, visible edema develops due to increasing capillary transparency, augmenting end-organ damages. "Classic" preeclampsia is a severe and quickly progressing condition with placental insufficiency and consequent fetal growth restriction and oligohydramnios. The outcome of this condition often leads to fetal hypoxia, eclampsia or placental abruption. The management is limited to a diligent prolongation of pregnancy to accomplish improved neonatal pulmonary function, careful diminishing high blood pressure, and delivery induction in due time. The other subtype, associated with relaxed vasculature and high cardiac output, is a maternal disease, in which obesity is an important risk factor since predisposes to enhanced water retention, hypertension, and a weakened endothelial dysfunction. Initially, enhanced water retention leads to lowered extremity edema, which oftentimes progresses to a generalized form and hypertension. In several cases, proteinuria appears most likely due to tissue edema. This condition already fully meets preeclampsia criteria. Laboratory alterations, including proteinuria, are modest and platelet count remains within the normal range. Fetal weight is also normal or frequently over average due to enhanced placental blood supply. It is very likely, further water retention leads to venous congestion, a parenchyma stasis, responsible for ascites, eclampsia, or placental abruption. During the management of this hypervolemia-associated preeclampsia, the administration of diuretic furosemide treatment seemingly offers promise.
Topics: Abruptio Placentae; Diuretics; Eclampsia; Female; Humans; Hypertension; Infant, Newborn; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; Water
PubMed: 35661540
DOI: 10.1016/j.ejogrb.2022.05.033 -
Journal of Epidemiology Nov 2021
Topics: Cholelithiasis; Creatinine; Humans; Proteinuria
PubMed: 34421082
DOI: 10.2188/jea.JE20210281 -
Pediatric Nephrology (Berlin, Germany) Oct 2021Studies have shown that losartan reduces serum uric acid in adults, unlike angiotensin-converting enzyme inhibitors. A previous study demonstrated that losartan and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Studies have shown that losartan reduces serum uric acid in adults, unlike angiotensin-converting enzyme inhibitors. A previous study demonstrated that losartan and enalapril had comparable effects on proteinuria in children.
METHODS
We conducted a post hoc analysis of results from a prospective trial in which the proteinuria-reducing effects of losartan and enalapril were compared. We have now evaluated (a) the effects of these medications on SUA in 248 children with proteinuria and (b) the correlation between changes in SUA and eGFR.
RESULTS
SUA levels after 36 months were found to be increased when compared to baseline in both losartan and enalapril groups. The mean change in SUA from baseline was significantly different at 12 months between 23 hypertensive patients randomised to losartan (3.69% decrease [95% CI 11.31%, 3.93%]) and 24 randomised to enalapril (12.57% increase [95% CI 3.72%, 21.41%]), p = 0.007. This significant difference remained after 24, 30 and 36 months but was observed in the entire group of 248 patients only at 12 months. There was a statistically significant negative correlation between changes in SUA and changes in eGFR at each time point over 36 months.
CONCLUSIONS
Losartan may have long-term beneficial effects on SUA and eGFR in children with proteinuria.
Topics: Adult; Antihypertensive Agents; Child; Enalapril; Glomerular Filtration Rate; Humans; Hypertension; Losartan; Prospective Studies; Proteinuria; Uric Acid
PubMed: 33881639
DOI: 10.1007/s00467-021-05045-4 -
American Journal of Kidney Diseases :... Jan 2022Evaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand...
RATIONALE & OBJECTIVE
Evaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand the association between changes in kidney parameters and cardiovascular disease risk.
STUDY DESIGN
Prospective cohort study.
SETTING & PARTICIPANTS
Annual visit data from 2,438 participants in the Chronic Renal Insufficiency Cohort (CRIC).
EXPOSURES
Average and slope of eGFR and UPCR in time-updated, 1-year exposure windows.
OUTCOMES
Incident heart failure, atherosclerotic cardiovascular disease events, death, and a composite of incident heart failure, atherosclerotic cardiovascular disease events, and death.
ANALYTICAL APPROACH
A landmark analysis, a dynamic approach to survival modeling that leverages longitudinal, iterative profiles of laboratory and clinical information to assess the time-updated 3-year risk of adverse cardiovascular outcomes.
RESULTS
Adjusting for baseline and time-updated covariates, every standard deviation lower mean eGFR (19mL/min/1.73m) and declining slope of eGFR (8mL/min/1.73m per year) were independently associated with higher risks of heart failure (hazard ratios [HRs] of 1.82 [95% CI, 1.39-2.44] and 1.28 [95% CI, 1.12-1.45], respectively) and the composite outcome (HRs of 1.32 [95% CI, 1.11-1.54] and 1.11 [95% CI, 1.03-1.20], respectively). Every standard deviation higher mean UPCR (136mg/g) and increasing UPCR (240mg/g per year) were also independently associated with higher risks of heart failure (HRs of 1.58 [95% CI, 1.28-1.97] and 1.20 [95% CI, 1.10-1.29], respectively) and the composite outcome (HRs of 1.33 [95% CI, 1.17-1.50] and 1.12 [95% CI, 1.06-1.18], respectively).
LIMITATIONS
Limited generalizability of annual eGFR and UPCR assessments; several biomarkers for cardiovascular disease risk were not available annually.
CONCLUSIONS
Using the landmark approach to account for time-updated patterns of kidney function, average and slope of eGFR and proteinuria were independently associated with 3-year cardiovascular risk. Short-term changes in kidney function provide information about cardiovascular risk incremental to level of kidney function, representing possible opportunities for more effective management of patients with chronic kidney disease.
Topics: Cohort Studies; Glomerular Filtration Rate; Humans; Prospective Studies; Proteinuria; Renal Insufficiency, Chronic; Risk Factors
PubMed: 34052355
DOI: 10.1053/j.ajkd.2021.03.021 -
Medicine May 2021To investigate the clinicopathological features and outcomes of primary IgA nephropathy with nephrotic-range proteinuria in Chinese children. Patients with biopsy-proven... (Observational Study)
Observational Study
To investigate the clinicopathological features and outcomes of primary IgA nephropathy with nephrotic-range proteinuria in Chinese children. Patients with biopsy-proven IgA nephropathy and nephrotic-range proteinuria between January 2011 and December 2017 were included, and their proteinuria and renal function were followed up. A total of 90 patients were enrolled, and 21.1% (19/90) of them had decreased renal function at diagnosis. Complete remission, partial remission, and no response of proteinuria occurred in 88.6% (70/79), 10.1% (8/79), and 1.3% (1/79), respectively, of the 79 patients who were followed up for 6 to 104 months. 73.7% (14/19) of the patients with decreased renal function at diagnosis recovered to normal level while 26.3% (5/19) of them did not recover or progressed to end-stage renal disease. Two patients with normal renal function at diagnosis progressed to renal insufficiency during follow-up period. By multivariate analysis, the risk for renal function deterioration was significantly higher in the partial remission and no response groups than in the complete remission group. Remission of proteinuria was important for improving renal prognosis in children with IgA nephropathy and nephrotic-range proteinuria. The outcomes for pediatric patients appeared to be better than that reported in adults.
Topics: Adolescent; Biopsy; Child; Child, Preschool; China; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerular Mesangium; Glomerulonephritis, IGA; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Proteinuria; Remission Induction; Retrospective Studies; Treatment Outcome
PubMed: 34032732
DOI: 10.1097/MD.0000000000026050 -
International Journal of Molecular... May 2022We previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing...
We previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing glomerulosclerosis in 5/6 nephrectomy rats. We therefore assessed the effects of long-term intervention with ARB vs. nonspecific antihypertensives in this study. Adult rats underwent 5/6 nephrectomy and renal biopsy 8 weeks later. The rats were then divided into three groups with equivalent renal function and glomerular sclerosis and treated with high-dose losartan (ARB), nonspecific antihypertensive triple-therapy (TRX), or left untreated (Control) until week 30. We found that blood pressure, serum creatinine levels, and glomerulosclerosis were lower at sacrifice in ARB and TRX vs. Control. Only ARB reduced proteinuria and maintained the density of WT-1-positive podocytes. Glomerular tufts showed more double-positive cells for CD44, a marker of activated parietal epithelial cells, and synaptopodin after ARB vs. TRX or Control. ARB treatment reduced aldosterone levels. ARB-treated rats had significantly improved survival when compared with TRX or Control. We conclude that both long-term ARB and triple-therapy ameliorate progression, but do not sustain the regression of glomerulosclerosis. ARB resulted in the superior preservation of podocyte integrity and decreased proteinuria and aldosterone, linked to increased survival in the uremic environment.
Topics: Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Kidney Diseases; Podocytes; Proteinuria; Rats
PubMed: 35682697
DOI: 10.3390/ijms23116018