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Transplantation Proceedings Mar 2022Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in...
BACKGROUND
Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake.
METHODS
We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records.
RESULTS
A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n = 163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m (IQR, 25 mL/min/1.73 m). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P = .008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis.
CONCLUSIONS
The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome.
Topics: Acidosis; Adolescent; Cross-Sectional Studies; Eating; Female; Hospitals, Teaching; Humans; Kidney Transplantation; Male; Prevalence; Proteinuria; Transplant Recipients
PubMed: 35125235
DOI: 10.1016/j.transproceed.2021.12.019 -
Swiss Medical Weekly 2017Albuminuria is strongly associated with renal and cardiovascular outcomes independently of renal function level. However, the pathophysiology of these associations is...
Albuminuria is strongly associated with renal and cardiovascular outcomes independently of renal function level. However, the pathophysiology of these associations is debated. In chronic kidney disease (CKD), phosphate retention participates in cardiovascular events and increased cardiovascular mortality. We hypothesised that albuminuria may modulate tubular phosphate handling by the kidney. To verify this hypothesis, we first studied the association between phosphataemia and albuminuria in children with nephrotic syndrome and in adults with CKD. In both cases, higher albuminuria was associated with higher phosphate level, independently of glomerular filtration rate. We further tried to decipher the molecular mechanisms of these observations. Using animal models of nephrotic proteinuria, we could show that albuminuric rats and mice had abnormally elevated sodium-phosphate apical co-transporter expression, despite elevated fibroblast growth factor 23 (FGF23). The FGF23 downstream pathway was inhibited despite elevated FGF23 levels. Klotho protein expression was also lower in proteinuric animals compared to controls. Finally, albumin had no direct effects on phosphate transport in cells. Altogether, we show that albuminuria induces alteration of phosphate tubular handling, independently of glomerular filtration rate. The mechanisms involved appear to include Klotho down-regulation and resistance to FGF23. This observation may link albuminuria to increased cardiovascular disease via altered phosphate handling. Finally, this observation opens up further opportunities to better understand the link between albuminuria, Klotho, FGF23 and phosphate handling.
Topics: Adult; Animals; Cardiovascular Diseases; Child; Disease Models, Animal; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Mice; Phosphates; Proteinuria; Rats; Renal Insufficiency, Chronic
PubMed: 29063524
DOI: 10.4414/smw.2017.14509 -
PloS One 2019Daily urine protein (UP) loss is a cumbersome but important measurement to guide diagnosis and treatment of renal disease. Spot urine protein-creatinine ratio (UPCR) can...
Daily urine protein (UP) loss is a cumbersome but important measurement to guide diagnosis and treatment of renal disease. Spot urine protein-creatinine ratio (UPCR) can been applied to estimate daily proteinuria. However, the correlations between spot and 24h proteinuria remain controversial. In this cross-sectional study, simultaneous collection of 24h and spot urines were performed from 1,039 (derivation cohort) and 204 CKD patients (validation cohort) of Chang Gung Memorial Hospital, from 2007 to 2017. The correlations between spot UPCR and 24h proteinuria were compared. The mean age of patients of derivation and validation cohort was 63 and 55 years and the mean estimated glomerular filtration rate was 62 ± 35 and 59 ± 36 mL/min/m2, respectively. The correlation coefficient was 0.819 between UPCR and 24hUP. Prediction equation was derived as: Log1024hUP (g) = 0.814 x Log10UPCR (mg/mg) + 0.110 x Gender- 0.004 x Age + 0.004 x Body weight (kg) + 0.002 x CKD stage coefficient- 0.018, where CKD stage coefficient: CKD stage G1 = 1, G2 = 2, G3a = 3.1, G3b = 3.2, G4 = 4, G5 = 5. Correlation coefficient between measured and predicted 24hUP among derivation group and validation group is 0.866 and 0.915, respectively. However, the agreement of spot and daily estimates was less pronounced with proteinuria > 3g than lower values in Bland-Altman analysis. Spot UPCR can accurately predict 24hUP in patients with daily proteinuria below 3g. The development of this equation may facilitate estimation of 24hUP in the clinical practice.
Topics: Age Factors; Aged; Area Under Curve; Creatinine; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Linear Models; Male; Middle Aged; Proteinuria; ROC Curve; Renal Insufficiency, Chronic; Severity of Illness Index; Sex Factors
PubMed: 30939176
DOI: 10.1371/journal.pone.0214614 -
Journal of Feline Medicine and Surgery Jun 2023The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats.
OBJECTIVES
The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats.
METHODS
A cross-sectional, case-control study was conducted on 44 client-owned cats with CS that were prospectively enrolled and evaluated for a Comprehensive Oral Health Assessment and Treatment at one of four institutions. Renal function was assessed with measurement of serum creatinine, urea nitrogen, serum symmetric dimethylarginine, urinalysis, urine protein:creatinine ratio and urine protein electrophoresis. Affected gingiva was biopsied to confirm the diagnosis of stomatitis. Renal biochemical analyses from the experimental group were compared with those of 44 age-matched controls without CS enrolled prospectively or retrospectively after presenting to the primary institution for routine healthcare. Control cats were included if they were clinically stable, their chronic illnesses were well managed and minimal dental disease was present on examination. Renal biomarkers were compared between groups using a -test or the Mann-Whitney U-test. Frequency of azotemia, proteinuria and the clinical diagnosis of renal disease were compared using Fisher's exact test.
RESULTS
Relative to the control group, cats in the CS group had significantly lower serum creatinine ( <0.001) and albumin concentrations ( <0.001), urine specific gravity ( = 0.024) and hematocrit ( = 0.003), and higher serum phosphorus ( <0.001), potassium ( <0.001) and globulin concentrations ( <0.001), white blood cell count ( <0.001) and urine protein:creatinine ratio ( = 0.009). There were no significant differences in serum symmetric dimethylarginine or urea nitrogen concentrations. No clinically significant findings were noted on urine protein electrophoresis. There were no significant differences in the frequency of azotemia, proteinuria or renal disease categories between the two groups.
CONCLUSIONS AND RELEVANCE
The present study does not demonstrate a significant difference in the frequency of kidney disease between cats with and without CS. Longitudinal evaluation is warranted to investigate the relationship between renal disease and CS.
Topics: Cats; Animals; Azotemia; Creatinine; Retrospective Studies; Case-Control Studies; Cross-Sectional Studies; Kidney; Proteinuria; Acute Kidney Injury; Biomarkers; Urea; Cat Diseases
PubMed: 37350300
DOI: 10.1177/1098612X231179883 -
Transplantation Proceedings Jun 2022Living donor kidney transplant represents the best treatment option for patients with end-stage kidney disease; however, it has been associated with possible risks to...
BACKGROUND
Living donor kidney transplant represents the best treatment option for patients with end-stage kidney disease; however, it has been associated with possible risks to the donor. Our aim was to evaluate the impact of kidney donation in the donor's estimated glomerular filtration rate (eGFR), blood pressure, and proteinuria and related risk factors.
PATIENTS AND METHODS
A single-center, retrospective study, including all living donors who underwent nephrectomy between January 2000 and December 2019, was performed. Demographic, clinical, and laboratory data were collected. Risk factors for a decrease in eGFR >30 mL/min/1.73 m one year after donation were assessed.
RESULTS
Eighty-six donors were included with a mean age of 46.7 ± 9.07 years. The mean follow-up was 105.6 ± 65.4 months, and 35 patients (41%) had more than 10 years of follow-up. No significant difference was found in proteinuria or body mass index (P > .1) before and after the donation. The prevalence of hypertension was higher after kidney donation (9.3% vs 22.1%; P < .001). A mean reduction in the eGFR in the first year of 37 ± 12 mL/min/1.73 m, followed by stabilization in the following years, was observed. The only variable that was significantly associated with a decline in GFR >30 mL/min/1.73 m was a lower predonation eGFR, with a cutoff value established at 100 mL/min/1.73 m for our sample.
DISCUSSION
Living donor nephrectomy appears to be an acceptably safe intervention. Predonation eGFR influences the adaptative response after nephrectomy; however, other variables did not have an impact on long-term outcome in our population.
Topics: Adult; Glomerular Filtration Rate; Humans; Kidney; Living Donors; Middle Aged; Nephrectomy; Proteinuria; Retrospective Studies
PubMed: 35599204
DOI: 10.1016/j.transproceed.2022.04.009 -
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 -
Journal of Hypertension Jan 2022The excess risk of atrial fibrillation in relation to the presence of proteinuria associated with hypertension has not been well elucidated. We aimed to determine the...
OBJECTIVE
The excess risk of atrial fibrillation in relation to the presence of proteinuria associated with hypertension has not been well elucidated. We aimed to determine the effect of hypertension and/or proteinuria on the incidence of atrial fibrillation. Second, we evaluated whether the associations with temporal changes in proteinuria status on the incidence of atrial fibrillation.
METHODS AND RESULTS
A total of 85 434 participants with hypertension and 125 912 participants without hypertension with age at least 60 years from the Korea National Health Insurance Service-Senior cohort were included. Amongst controls (participants without proteinuria and hypertension), hypertension only, proteinuria only, and hypertension with proteinuria groups, the adjusted incidences of atrial fibrillation were 0.51, 0.69. 0.78 and 0.99 per 100 person-years, respectively after inverse probability of treatment weighting. Compared with controls, the weighted risks of atrial fibrillation in the hypertension only, proteinuria only and hypertension with proteinuria groups were increased by 37% (hazard ratio 1.37, 95% confidence interval, CI 1.30-1.44, P = 0.001), 55% (hazard ratio 1.55, 95% CI 1.28-1.88, P < 0.001), and 98% (hazard ratio 1.98, 95% CI 1.62-2.43, P < 0.001), respectively. Populations who had proteinuria in the first examination had an increased risk of atrial fibrillation even in the group whereby the proteinuria was resolved on the second examination (hazard ratio 1.36, 95% CI 1.12-2.31, P < 0.001). The presence of proteinuria in first and second analysis had the highest risk of incident atrial fibrillation (hazard ratio 1.61, 95% CI 1.12-2.31).
CONCLUSION
In conclusion, hypertension and/or proteinuria were associated with increased risk of atrial fibrillation, with the greatest risks when both are present. Proteinuria could be a useful factor for predicting atrial fibrillation development.
Topics: Aged; Atrial Fibrillation; Cohort Studies; Humans; Hypertension; Incidence; Proteinuria; Risk Factors
PubMed: 34857705
DOI: 10.1097/HJH.0000000000002987 -
Kidney & Blood Pressure Research 2020Obesity has become a major public health problem, and the prevalence of kidney diseases has increased in parallel. Among kidney diseases caused by metabolic disorders,... (Review)
Review
BACKGROUND
Obesity has become a major public health problem, and the prevalence of kidney diseases has increased in parallel. Among kidney diseases caused by metabolic disorders, obesity-related glomerulopathy (ORG) is secondary to obesity.
SUMMARY
ORG is mainly caused by glomerular hyperfiltration, dysregulation of hormone and cytokine secretion in adipose tissues, and ectopic lipid accumulation in renal cells. ORG is pathologically characterized by glomerular hypertrophy, with or without focal and segmental glomerulosclerosis. Patients with ORG usually present with proteinuria concomitant with metabolic disorders such as dyslipidemia and hypertension. Weight loss, RAAS inhibitors, and improved insulin resistance can reduce the progression of ORG.
CONCLUSION
ORG is a growing renal pathological change in obese individuals, and a comprehensive understanding of the disease is pivotal to avoid its occurrence and improve quality of life for those with obesity. Key Messages:This review comprehensively describes the characteristics of ORG in pathological changes, clinical manifestations, pathogeneses and treatments.
Topics: Animals; Glomerulosclerosis, Focal Segmental; Humans; Hypertrophy; Kidney Glomerulus; Obesity; Proteinuria
PubMed: 32498064
DOI: 10.1159/000507784 -
Clinical Journal of the American... Mar 2019Data are scarce on blood metabolite associations with proteinuria, a strong risk factor for adverse kidney outcomes. We sought to investigate associations of proteinuria... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
Data are scarce on blood metabolite associations with proteinuria, a strong risk factor for adverse kidney outcomes. We sought to investigate associations of proteinuria with serum metabolites identified using untargeted profiling in populations with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Using stored serum samples from the African American Study of Kidney Disease and Hypertension (AASK; =962) and the Modification of Diet in Renal Disease (MDRD) study (=620), two rigorously conducted clinical trials with per-protocol measures of 24-hour proteinuria and GFR, we evaluated cross-sectional associations between urine protein-to-creatinine ratio and 637 known, nondrug metabolites, adjusting for key clinical covariables. Metabolites significantly associated with proteinuria were tested for associations with CKD progression.
RESULTS
In the AASK and the MDRD study, respectively, the median urine protein-to-creatinine ratio was 80 (interquartile range [IQR], 28-359) and 188 (IQR, 54-894) mg/g, mean age was 56 and 52 years, 39% and 38% were women, 100% and 7% were black, and median measured GFR was 48 (IQR, 35-57) and 28 (IQR, 18-39) ml/min per 1.73 m. Linear regression identified 66 serum metabolites associated with proteinuria in one or both studies after Bonferroni correction (<7.8×10), 58 of which were statistically significant in a meta-analysis (<7.8×10). The metabolites with the lowest values (<10) were 4-hydroxychlorthalonil and 1,5-anhydroglucitol; all six quantified metabolites in the phosphatidylethanolamine pathway were also significant. Of the 58 metabolites associated with proteinuria, four were associated with ESKD in both the AASK and the MDRD study.
CONCLUSIONS
We identified 58 serum metabolites with cross-sectional associations with proteinuria, some of which were also associated with CKD progression.
PODCAST
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_02_07_CJASNPodcast_19_03_.mp3.
Topics: Black or African American; Biomarkers; Clinical Trials as Topic; Cross-Sectional Studies; Disease Progression; Energy Metabolism; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Metabolomics; Middle Aged; Proteinuria; Renal Insufficiency, Chronic; United States
PubMed: 30733224
DOI: 10.2215/CJN.10010818 -
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