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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 -
The Journal of Clinical Investigation Jan 2020Albuminuria acts as a marker of progressive chronic kidney disease and as an indicator for initiation of hypertension treatment via modulation of the...
Albuminuria acts as a marker of progressive chronic kidney disease and as an indicator for initiation of hypertension treatment via modulation of the renin-angiotensin-aldosterone system with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors. However, the true significance of albuminuria has yet to be fully defined. Is it merely a marker of underlying pathophysiology, or does it play a causal role in the progression of kidney disease? The answer remains under debate. In this issue of the JCI, Bedin et al. used next-generation sequencing data to identify patients with chronic proteinuria who had biallelic variants in the cubilin gene (CUBN). Through investigation of these pathogenic mutations in CUBN, the authors have further illuminated the clinical implications of albuminuria.
Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Humans; Proteinuria; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 31793908
DOI: 10.1172/JCI133250 -
The Journal of Small Animal Practice Dec 2023To assess relationships between urine sediment and microbial culture findings and the presence of proteinuria in canine urine samples, and to assess the change in the...
OBJECTIVES
To assess relationships between urine sediment and microbial culture findings and the presence of proteinuria in canine urine samples, and to assess the change in the percentage of proteinuric samples and urine protein-to-creatinine ratio when urine abnormalities resolve.
MATERIALS AND METHODS
Canine urine samples collected via cystocentesis and submitted for culture and contemporaneous urinalysis (including urine protein-to-creatinine ratio) were retrospectively identified. Dogs receiving corticosteroids were excluded. Associations between haematuria (red blood cells>5/high-power field), pyuria (white blood cells>5/high-power field), presence of microorganisms on microscopy, active sediment, and positive culture and proteinuria (urine protein-to-creatinine ratio>0.5) were investigated. Patient characteristics were considered possible confounders. In dogs with repeat urinalysis, the associations between active sediment and positive culture resolution on proteinuria and urine protein-to-creatinine ratio were assessed.
RESULTS
One hundred and ninety-two of 491 samples were proteinuric (39.1%). Age was positively associated with proteinuria. In the multivariable analysis corrected for age, active sediment was the only variable significantly associated with proteinuria (adjusted odds ratio: 2.12; 95% confidence interval: 1.44 to 3.11); however, only 49.8% of samples with active sediment were proteinuric. Neither resolution of active sediment nor positive culture were associated with reduced proportions of proteinuric samples (from 57.9% to 42.1% and from 40.0% to 25.0%, respectively) or significant reductions in urine protein-to-creatinine ratio (median change: -0.16 and -0.14, respectively).
CLINICAL SIGNIFICANCE
Attributing proteinuria to urinalysis abnormalities or a positive urine culture in canine cystocentesis samples is not supported by our findings, and could result in alternative causes of proteinuria (e.g. renal proteinuria) being overlooked.
Topics: Humans; Dogs; Animals; Creatinine; Retrospective Studies; Dog Diseases; Urinalysis; Proteinuria
PubMed: 37632274
DOI: 10.1111/jsap.13669 -
Biomolecules May 2023Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to...
Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to identify renal dysfunction in candidates for bariatric surgery. To reduce the sources of bias, subjects with diabetes, prediabetes under metformin treatment, neoplastic or inflammatory diseases were excluded. Patients' (n = 192) average body mass index was 41.7 ± 5.4 kg/m. Among these, 51% (n = 94) had creatinine clearance over 140 mL/min, 22.4% (n = 43) had proteinuria over 150 mg/day and 14.6% (n = 28) albuminuria over 30 mg/day. A creatinine clearance higher than 140 mL/min was associated with higher levels of proteinuria and albuminuria. Univariate analysis identified sex, glycated hemoglobin, uric acid, HDL and VLDL cholesterol as being associated with albuminuria, but not with proteinuria. On multivariate analysis, glycated hemoglobin and creatinine clearance as continuous variables were significantly associated with albuminuria. In summary, in our patient population prediabetes, lipid abnormalities and hyperuricemia were associated with albuminuria, but not with proteinuria, suggesting different disease mechanisms might be implicated. Data suggest that in obesity-associated kidney disease, tubulointerstitial injury precedes glomerulopathy. A significant proportion of obesity surgery candidates present clinically relevant albuminuria and proteinuria along with renal hyperfiltration, suggesting that routine pre-operative assessment of these parameters should be considered.
Topics: Humans; Albuminuria; Prediabetic State; Glycated Hemoglobin; Creatinine; Glomerular Filtration Rate; Proteinuria; Kidney Diseases; Bariatric Surgery; Obesity; Phenotype
PubMed: 37238660
DOI: 10.3390/biom13050790 -
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 -
BMC Pregnancy and Childbirth Aug 2023HELLP syndrome refers to a group of clinical syndromes characterized by hemolysis, elevated liver enzymes and low platelet, and the evidence on the association between...
BACKGROUND
HELLP syndrome refers to a group of clinical syndromes characterized by hemolysis, elevated liver enzymes and low platelet, and the evidence on the association between proteinuria and the severity of HELLP and its maternal and neonatal outcomes is rare.
METHODS
106 pregnant women were assigned to the proteinuric group (24-hUPro ≥ 0.3 g, 79 cases) and the non-proteinuric group (24-hUPro < 0.3 g, 27 cases). The proteinuric group was further divided into three subgroups: mild group (24-hUPro:0.3-2.0 g, 33 cases), moderate group (24-hUPro:2.0-5.0 g, 21 cases) and severe group (24-hUPro: ≥5.0 g, 25 cases). The general clinical data, laboratory indexes, complications and pregnancy outcome and adverse neonatal outcomes of HELLP with or without proteinuric were analyzed.
RESULTS
Compared with proteinuric group, the non-albuminuric group or in the three proteinuric subgroups of HELLP pregnant women's, increased proteinuria was associated with earlier onset gestations, higher incidence of abdominal pain, skin jaundice, headache, blurred vision (p < 0.05 respectively), and also the higher levels of ALT, AST, LDH, Fib, APTT, ATII, proportions of tubular urine and lower levels of ALB, PLT (p < 0.05 respectively). In the three subgroups of the proteinuric group, the ratio of fetal growth restriction, cesarean section and postpartum hemorrhage were compared, and the difference was statistically significant (p < 0.05 respectively). Compared with the proteinuric group, the non-proteinuric group had higher birth weight, birth length, and lower SGA, admission rate in NICU (p < 0.05 respectively). In the three subgroups of the proteinuric group, significant differences were identified in the adverse outcomes of newborns (p < 0.05 respectively), and the incidence of adverse outcomes in neonates tended to be higher. Significant differences were identified in birth weight, birth length, and lower SGA and NICU occupancy rate among the three subgroups (p < 0.05 respectively).
CONCLUSIONS
HELLP syndrome is a severe complication of pregnancy, involving multiple systems of the whole body. It has posed a great challenge to obstetricians for its acute onset, dangerous condition, rapid progress, and great harm. Thus, insights into HELLP syndrome should be gained, and early diagnosis, early treatment and timely termination of pregnancy should be conducted to reduce the incidence of maternal and fetal adverse outcomes and improve maternal and fetal prognosis.
Topics: Infant, Newborn; Humans; Female; Pregnancy; HELLP Syndrome; Birth Weight; Cesarean Section; Proteinuria; Family
PubMed: 37596554
DOI: 10.1186/s12884-023-05862-5 -
Progress in Transplantation (Aliso... Dec 2021Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact... (Observational Study)
Observational Study
Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.
Topics: Adult; Cardiovascular Diseases; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Proportional Hazards Models; Proteinuria; Risk Factors; Transplant Recipients
PubMed: 34839728
DOI: 10.1177/15269248211046011 -
Journal of Veterinary Internal Medicine Mar 2021Proteinuria is an independent risk factor for morbidity and mortality in dogs. An association between proteinuria and gallbladder mucocele formation in dogs is unknown.
BACKGROUND
Proteinuria is an independent risk factor for morbidity and mortality in dogs. An association between proteinuria and gallbladder mucocele formation in dogs is unknown.
OBJECTIVE
Determine if gallbladder mucocele formation or clinicopathologic comorbidities are associated with proteinuria.
ANIMALS
Twenty-five dogs with mucocele formation and 25 breed and age-matched control dogs from a prior study.
METHODS
Retrospective case control study. Proteinuria defined by calculated urine dipstick protein concentration (mg/mL) to urine specific gravity (USG) ratio. Clinicopathologic findings, postcosyntropin cortisol concentration, thyroid function profile, and illness severity score were recorded.
RESULTS
Median urine dipstick protein concentration to USG ratio and number of dogs having a ratio ≥1.5 were significantly higher for dogs with mucocele formation compared to control dogs. Proteinuria was not significantly associated with CBC or serum biochemistry profile abnormalities but increased in relation to severity of illness.
CONCLUSIONS AND CLINICAL IMPORTANCE
Gallbladder mucocele formation is significantly associated with proteinuria in dogs. Diagnosis and treatment of proteinuria in dogs with mucocele formation might minimize long term kidney morbidity in these patients.
Topics: Animals; Case-Control Studies; Dog Diseases; Dogs; Gallbladder; Mucocele; Proteinuria; Retrospective Studies
PubMed: 33547696
DOI: 10.1111/jvim.16051 -
Kidney International Jan 2020Immune checkpoint inhibitors have dramatically improved cancer therapy for many patients. These humanized monoclonal antibodies against various immune checkpoints... (Review)
Review
Immune checkpoint inhibitors have dramatically improved cancer therapy for many patients. These humanized monoclonal antibodies against various immune checkpoints (receptors and ligands) effectively treat a number of malignancies by unleashing the immune system to destroy cancer cells. These drugs are not excreted by the kidneys or liver, have a long half-life, and undergo receptor-mediated clearance. Although these agents have greatly improved the prognosis of many cancers, immune-related end organ injury is a complication that has come to light in clinical practice. Although less common than other organ involvement, kidney lesions resulting in acute kidney injury and/or proteinuria are being described. Acute tubulointerstitial nephritis is the most common lesion seen on kidney biopsy, while acute tubular injury and glomerular lesions occur less commonly. Clinical findings and laboratory tests are suboptimal in predicting the underlying renal lesion, making kidney biopsy necessary in the majority of cases to definitely diagnose the lesion and potentially guide therapy. Immune checkpoint inhibitor discontinuation and corticosteroid therapy are recommended for acute tubulointerstitial nephritis. Based on a handful of cases, re-exposure to these drugs in patients who previously developed acute tubulointerstitial nephritis has been mixed. Although it is unclear whether re-exposure is appropriate, it should perhaps be considered in patients with limited options. When this approach is taken, patients should be closely monitored for recurrence of acute kidney injury. Treatment of cancer in patients with a kidney transplant with immune checkpoint inhibitors risks the development of acute rejection in some patients and requires close surveillance.
Topics: Acute Kidney Injury; Antineoplastic Agents, Immunological; Graft Rejection; Humans; Immune Checkpoint Inhibitors; Kidney Glomerulus; Kidney Transplantation; Neoplasms; Proteinuria
PubMed: 31685311
DOI: 10.1016/j.kint.2019.07.022 -
Scientific Reports Nov 2023We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional,... (Clinical Trial)
Clinical Trial
We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of registration 14/02/2020). Patients were treated with Budesonide at a dose of 9 mg/day for 12 months, subsequently tapered to 3 mg/day for another 12 months. The primary endpoints were change of eGFR and proteinuria at 12, 24 and 36 months. The study cohort had a mean eGFR and 24-h proteinuria of 59 ± 24 ml/min/1.73m and 1.89 ± 1.5 g/day, respectively. Treatment with budesonide determined a reduction in proteinuria at 12-, 24- and 36-months by -32.9% (95% CI - 53.6 to - 12.2), - 49.7% (95% CI - 70.1 to - 29.4) and - 68.1% (95% CI - 80.6 to - 55.7). Budesonide determined an eGFR preservation corresponding to a 12-, 24- and 36-months change of + 7.68% (95% CI - 4.7 to 20.1), + 7.42% (95% CI - 7.23 to 22.1) and + 4.74% (95%CI - 13.5 to 23), respectively. The overall eGFR change/year was + 0.83 ml/min/y (95% CI - 0.54 to 4.46). Budesonide was well-tolerated, and treatment emergent adverse events were mostly mild in severity and reversible. Budesonide was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria and preserving renal function over 36 months of therapy.
Topics: Humans; Budesonide; Glomerulonephritis, IGA; Prospective Studies; Glomerular Filtration Rate; Proteinuria
PubMed: 37978255
DOI: 10.1038/s41598-023-47393-1