Influence Of Proteinuria Research Articles

#5532 COVID-19 INFECTION MODIFIES GLOMERULAR DISEASE EVOLUTION

Abstract Background and Aims A fibrotic effect of the SARS-Cov2 virus (Covid-19) has been described and the risk for acute renal failure in glomerular disease (GD) patients; however, the long-term renal effect in these patients is unknown. We evaluate the impact of the Covid-19 infection on eGFR, the influence of proteinuria, the effect of the drugs used to control glomerulonephritis and the use of Paxlovid (nirmatrelvir/ritonavir) for covid infection control. Method We retrospectively evaluate the eGFR (mL/min/1.73m2) at month 12 and 6 before infection (pre-infection period), during infection, 6 months after infection and at the last visit post-infection in renal biopsy-proven glomerulonephritis patients. Patients were included from January/2020 to July/2022. All patients were followed up for six months or more from infection. Results Forty-seven patients were included. The mean follow-up was 13 months (min: 6-max = 33). Sex Female 24 (52%), Age (mean[SD]) = 47 (14) years. 39(85%) were vaccinated before infection. At infection time, 31(66%) of the patients presented proteinuria (protein/creatinine ratio > 0,2 mg/mg). 27(54%) received oral steroids, 27(54%) mycophenolate, 24(51%) prednisone, and 27(54%) renin-angiotensin system inhibitors (RASi). Four (8%) started chronic renal replacement therapy during the follow-up, and 12(25%) required hospital admission. During the pre-infection period, eGFR remained stable (mean change (95%CI): -2.2 (-8.2 to 3.7) mL/min/1.73m2, P = 1. Compared with month six before infection, eGFR decreased at the end of the follow-up by 9.1 (95% CI: 0.96 to 17.2) mL/min/1.73m2, P = 0.019. After stratifying by the presence of proteinuria, eGFR decreased only in those with proteinuria 14.5 (95%CI: 3.7 to 25.4) mL/min/1,73m2, while no changes were observed in those without proteinuria. No changes in proteinuria level after infection were observed. No interaction between drugs used, hospitalisation requirements and eGFR evolution was observed. In the sub-group of patients treated with Paxlovid (all previously vaccinated) after six months of follow-up, no patients required hospitalisation; however, eGFR evolution was similar to the whole group, which decreased only in those with proteinuria at baseline. Conclusion The Covid-19 infection in proteinuric GD patients changed the renal function evolution dramatically. The medication used (mycophenolate, steroid and RASi), including Paxlovid, did not influence this evolution. At the end of the follow-up, the accelerated renal function deterioration continues. Urgent therapeutic measures for controlling eGFR decline in these patients are needed.

Influence of preanalytic and analytic variables in canine and feline urine specific gravity measurement by refractometer.

Urine specific gravity (USG), which is usually measured by refractometry, is an important indicator of renal concentrating ability. Few studies have evaluated refractometers with separate scales for canine and feline urine. Variables such as protein content or storage time may influence the USG. We compared the effects of measuring USG with a refractometer with single or separate scales for canine and feline urine, investigated inter- and intra-observer variability, and measured agreement between whole urine and supernatant. We evaluated the correlation between USG and osmolality, the influence of urinary protein on USG and osmolality, and the impact of storage time up to 6 mo. We examined 252 canine and 126 feline samples. Bland-Altman analysis revealed higher USG values of the single-scale refractometer than the dual-scale refractometer, with a mean difference (bias) of < 0.001 for canine and 0.003 for feline specimens. Inter- and intra-observer variability were acceptable. Good agreement was shown between USG of whole urine and supernatant. Correlations between USG and osmolality were excellent (0.98-0.99, p < 0.001). Proteinuria up to 1 g/L had no major impact on USG or osmolality. Storage time had no significant effect on USG. The difference between the refractometers is clinically irrelevant, and the use of a refractometer with separate feline and canine scales is unnecessary. Whole urine and supernatant stored up to 6 mo can both be used for USG measurement. The influence of proteinuria <1 g/L on USG and osmolality is negligible.

Influence of Proteinuria and Blood Pressure on Apgar Scores and Fetal Birth Weight in Preeclampsia

Influence of Proteinuria and Blood Pressure on Apgar Scores and Fetal Birth Weight in Preeclampsia

Influence of Proteinuria on Glycated Albumin Values in Diabetic Patients with Chronic Kidney Disease

Glycated albumin (GA), which is an alternative glycemic marker, is influenced by factors associated with albumin turnover, and it is not clear whether proteinuria influences GA values in diabetic patients with chronic kidney disease (CKD). We enrolled 94 diabetic patients with CKD stages 3 to 5. GA, glycated hemoglobin, and urinary protein excretion (UP) levels were consecutively obtained in each patient. The correlations between GA and UP and those between changes in GA and UP were examined. There was a significant correlation between GA and UP in all cases (r=-0.46, p<0.0001), however no significant correlation was found in cases with UP of 0-3.49 g/day (r=0.01). GA values in cases with UP ≥3.5 g/day were significantly lower than those in cases with UP <3.5 g/day [UP ≥3.5 g/day and serum albumin (Alb) ≤3 g/dL; 12.0 ± 1.3%, UP ≥3.5 g/day and Alb >3 g/dL; 17.8 ± 4.3%, 0≥ UP <3.5 g/day; 21.2 ± 4.2%], while no significant difference in HbA(1c) or glucose levels was found. In cases with a minimum of UP ≥0.5 g/day, no significant correlation was found between the difference in GA and the difference in UP at the point of maximum UP and minimum UP (r=0.04). Nephrotic-range proteinuria decreases GA values independent of the glycemic state, while non-nephrotic range proteinuria has no significant influence on GA values in diabetic CKD patients.

Podocyte Injury Induced by Albumin Overload in vivo and in vitro: Involvement of TGF-Beta and p38 MAPK

Background: Proteinuria is a well-established exacerbating factor in chronic kidney disease. Although the mechanisms of albumin-induced tubulointerstitial damage have been extensively studied, the influence of proteinuria on podocytes has not been sufficiently elucidated. The present study examined the effect of albumin overload on podocytes in vivo and in vitro and explored the underlying mechanisms. Methods: Rat podocytes were exposed to albumin overload in vivo by the intraperitoneal injection of albumin over 2 days whilst cultured podocytes were subjected to albumin in vitro. We analyzed albumin uptake, podocyte apoptosis, staining for F-actin and nephrin and involvement of TGF-β1 and p38 MAPK cascades. Results: Rats administered albumin exhibited massive proteinuria and podocyte injury manifested by decreased nephrin immunostaining and foot process effacement. These abnormalities were accompanied by albumin deposition, TGF-β1 upregulation, p38 MAPK phosphorylation and an increased number of glomerular TUNEL-positive cells. Exposure of cultured podocytes to albumin caused actin disarrangement and apoptosis. Podocyte injury was preceded by albumin uptake, induction of TGF-β1 and phosphorylated p38 MAPK. Treatment of podocytes with anti-TGF-β1 neutralizing antibody or SB203580 significantly reduced the albumin-induced injury. Conclusions: These results indicate that albumin overload in vivo and in vitro promotes podocyte injury mainly via TGF-β1/p38 MAPK pathways.

Influence of proteinuria on cystatin C serum concentration in patients with primary glomerulonephritis

Influence of proteinuria on cystatin C serum concentration in patients with primary glomerulonephritis

Change in Serum Creatinine Levels Between 6 and 12 Months and Kidney Graft Survival: Influence of Proteinuria

Renal function within the first year after transplantation has been shown to be an important parameter influencing long-term survival. In this study, we examined the relationship between long-term outcome in 365 renal transplants and renal function in the first year, expressed as serum creatinine (SCr) level at 6 months and at 1 year as well as namely ΔCr, the change in SCr between 6 months and 1 year. In addition, we examined the influence of the presence of proteinuria as a predictive factor for a worse evolution. Graft survival was worse among patients with higher ΔCr, especially among those who developed proteinuria. In a Cox regression analysis of long-term graft survival, both ΔCr and proteinuria were important predictors of half-life. The risk of graft loss when ΔCr >0.3 was 2.65 (1.8–3.8; P < .000), whereas the risk increased to 5.67 (3.3–9.4; P < .00) when proteinuria was present. In conclusion, ΔCr values predict long-term graft survival. Patients who developed proteinuria were at higher risk for graft loss compared with those without proteinuria. By using a combination of SCr and ΔCr with proteinuria, it is possible to identify a subset of transplant recipients with a predictably shortened half-life.

Influence of proteinuria on disorders of lipoprotein metabolism

Influence of proteinuria on disorders of lipoprotein metabolism

Influence of proteinuria on disorders of lipoprotein metabolism

Summary: In order to assess the role of proteinuria in the development of lipoprotein metabolism derangements, we investigated 60 patients (32 males and 28 females, mean age 37.15 ± 9.85 years, average clearance of endogenous creatinine 86.27 ± 19.81 mL/min, average body mass index 24.18 ± 2.23 kg/m2), distributed in four groups according to degree of glomerular proteinuria. The control group, with urinary protein excretion 3.0 g/24h had significantly higher serum HDL cholesterol (p 3.0 g/24h as compared with patients with proteinuria ranging from 1.0 to 3.0 g/24h and control subjects (p<0.01). We therefore conclude that proteinuria causes disorders of LDL, VLDL, HDL and lipoprotein (a) metabolism.

Proteinuria after renal transplantation affects not only graft survival but also patient survival.

Proteinuria is associated with an increased risk of renal failure. Moreover, proteinuria is associated with an increased death risk in patients with diabetes mellitus or hypertension and even in the general population. One year after renal transplantation, we studied the influence of the presence of proteinuria on the risk of either graft failure or death in all 722 recipients of a kidney graft in our center who survived at least 1 year with a functioning graft. Proteinuria was analyzed both as a categorical variable (presence versus absence) and as a continuous variable (quantification of 24 hr urine). Other variables included in this analysis were: donor/recipient age and gender, original disease, race, number of HLA-A and HLA-B mismatches, previous transplants, postmortal or living related transplantation, and transplantation year. At 1 year after transplantation, we included: proteinuria, serum cholesterol, serum creatinine, blood pressure, and the use of antihypertensive medication. In the Cox proportional hazards analysis, proteinuria at 1 year after transplantation (both as a categorical and continuous variable) was an important and independent variable influencing all endpoints. The influence of proteinuria as a categorical variable on graft failure censored for death showed no interaction with any of the other variables. There was an adverse effect of the presence of proteinuria on the graft failure rate (RR=2.03). The influence of proteinuria as a continuous variable showed interaction with original disease. The presence of glomerulonephritis, hypertension, and systemic diseases as the original disease significantly increased the risk of graft failure with an increasing amount of proteinuria at 1 year. The influence of proteinuria as a categorical variable on the rate ratio for patient failure was significant, and there was no interaction with any of the other significant variables (RR=1.98). The death risk was almost twice as high for patients with proteinuria at 1 year compared with patients without proteinuria. The influence of proteinuria as a continuous variable was also significant and also without interaction with other variables. The death risk increased with increasing amounts of proteinuria at 1 year. Both the risks for cardiovascular and for noncardiovascular death were increased. Proteinuria after renal transplantation increases both the risk for graft failure and the risk for death.

Enzymuria and beta2-mikroglobulinuria in the assessment of the influence of proteinuria on the progression of glomerulopathies.

The important role of the tubulo-interstitial system for the progression of glomerulonephritis (GN), is the cause of a continuous search for the proper markers of kidney tubules damage, which can be applied in clinical diagnosis. In the present work the activity of N-acetyl-beta-D-glucosamidase (NAG), its isoenzyme NAG-B, alanylaminopeptidase (AAP), gamma-glutamyltransferase (GGT), concentration of beta2-microglobulin (beta2M) and daily protein excretion in the urine of 37 patients with morphologically different glomerulopathies were measured. The serum creatinine was also controlled. The obtained results suggest that activity of NAG in the patients with GN has an intermediate connection with proteinuria and could be a cause of the inflammatory process of the kidney, but the activity of AAP is directly dependent on urine protein concentration. Systemic analysis of both partial and multiple correlation coefficients of the examined indicators creates new, additional possibilities in the estimation of activity and progress of GN.

Influence of proteinuria on long-term outcome among patients with diabetes: The evidence continues to accumulate

Molecularly imprinted polymers (MIPs) rendered selective solely by the imprinting with protein templates lacking of distinctive properties to facilitate strong target-MIP interaction are likely to exhibit medium to low template binding affinities. While this prohibits the use of such MIPs for applications requiring the assessment of very low template concentrations, their implementation for the quantification of high-abundance proteins seems to have a clear niche in the analytical practice. We investigated this opportunity by developing a polyscopoletin-based MIP nanofilm for the electrochemical determination of elevated human serum albumin (HSA) in urine. As reference for a low abundance protein ferritin-MIPs were also prepared by the same procedure. Under optimal conditions, the imprinted sensors gave a linear response to HSA in the concentration range of 20–100 mg/dm3, and to ferritin in the range of 120–360 mg/dm3. While as expected the obtained limit of detection was not sufficient to determine endogenous ferritin in plasma, the HSA-sensor was successfully employed to analyse urine samples of patients with albuminuria. The results suggest that MIP-based sensors may be applicable for quantifying high abundance proteins in a clinical setting.

Effect of dietary protein restriction and influence of proteinuria on progression of type 2 diabetic renal failure

This study investigated the effect of dietary protein restriction on disease progression and how it is influenced by proteinuria in patients with type 2 diabetic nephropathy(DN) and renal failure. One hundred and six type 2 DN patients whose baseline creatinine clearance(Ccr) values were 29 +/- 12 ml/min/1.73 m2 were maintained on a diet containing 0.66 +/- 0.05 g/kg/day of protein. They were classified into 3 groups according to mean dietary protein intake(DPI) estimated from urinary urea nitrogen excretion during the follow-up period of 23 +/- 14 months(I, < 0.7 g/kg/day; II, 0.7-0.89 g/kg/day; III, > or = 0.9 g/kg/day). Furthermore, they were divided into 3 subgroups according to mean urinary protein excretion(UP) during the follow-up period (a, > or = 5.0 g/day; b, 2.0-4.99 g/day; c, < 2.0 g/day). Their rates of decline of Ccr(D-Ccr) and the changes in UP were examined. There were no significant differences in D-Ccr among Group Ia, IIa, and IIIa(1.1 +/- 0.6, 1.5 +/- 0.7, 1.2 +/- 0.6 ml/min/1.73 m2/month), among Group Ib, IIb, and IIIb(0.6 +/- 0.3, 0.7 +/- 0.4, 0.8 +/- 0.4 ml/min/1.73 m2/month), and also among Group Ic, IIc, and IIIc(0.1 +/- 0.3, 0.2 +/- 0.2, 0.2 +/- 0.6 ml/min/1.73 m2/month). On the other hand, significant differences were revealed in D-Ccr among Group Ia, Ib, and Ic, among Group IIa, IIb, and IIc, and among Group IIIa, IIIb, and IIIc. There were no significant differences in final UP and minimum UP during follow-up among 3 groups of different DPI levels in patients with 5.0 g/day < or = baseline UP(n = 49) and in patients with 2.0 < or = baseline UP < 5.0 g/day(n = 37). However, significant correlations were demonstrated between D-Ccr and the relative changes in UP between baseline and minimum during the follow-up period in both patients(r = 0.49, 0.48, p < 0.001, p < 0.01). Irrespective of the level of dietary protein restriction, proteinuria has a great influence on disease progression, and the reduction in UP correlates with retardation of renal function loss in patients with type 2 DN and renal failure.

Influence of proteinuria on long-term transplant survival in kidney transplant recipients.

Long-term prognosis in kidney transplant recipients depends on multiple factors. To investigate whether mild proteinuria within the first 6 months following transplantation is a determinant of the long-term function and survival of kidney transplants, 357 patients transplanted between 1980 and 1990 were retrospectively examined over a period of 5 years. 25.5% of the patients developed an early proteinuria between 0.25 and 1.0 g/day over 6 or more months. This group was well matched concerning gender, age of recipient, underlying disease, time on hemodialysis, donor age, cold ischemia time and HLA mismatches with the group without proteinuria (n = 266). Five-year transplant survival in the group with proteinuria was 58.9% in contrast to 85.6% in recipients without proteinuria. Intermittent proteinuria did not worsen long-term prognosis. Proteinuria of 12 months or longer further reduced 5-year transplant survival to 42.6%. Over the whole observation period, serum creatinine in recipients with proteinuria was about 0.5 mg/dl higher as compared with patients without proteinuria. No correlation between proteinuria and gender, age of recipient, duration of hemodialysis, age of donor, cold ischemia time and mismatches could be detected. In conclusion, early proteinuria apparently is not due to established donor or recipient factors. However, there is a strong correlation of proteinuria with worse transplant function and survival.

Late outcome of a controlled trial of enalapril treatment in progressive chronic renal failure. Hard end-points and influence of proteinuria

An earlier controlled trial showed that over an average of 26 months, enalapril slowed the progression of chronic renal failure. Following completion of the trial, the patients continued to receive antihypertensive treatment according to ordinary clinical criteria. All but four patients in the enalapril group remained on that drug, and two patients in the control group were switched to an angiotensin-converting enzyme (ACE) inhibitor. In the present study the fate of the 70 patients 44 months after termination of the trial was investigated, with a total follow-up of around 7 years. In the original enalapril group, 12 of the 35 patients (34%) were alive without renal replacement therapy versus five of the 35 patients (14%) in the control group. This difference of 20% in favour of having been in the enalapril group in the original trial was significant (P = 0.05; 95% confidence limits 0.5-39.5%). The influence of baseline proteinuria on clinical outcome was analysed. In the original control group, baseline renal clearances of albumin (Calb) and immunoglobulin G (CIgG) were significantly lower in patients surviving without renal replacement therapy at follow-up than in patients who ultimately developed end-stage renal failure (ESRF) (P < 0.05). In the original enalapril group, these baseline clearances were equal in the two renal outcome groups. In all patients, baseline Calb and CIgG were negatively correlated with the rate of change in GFR during the controlled trial (r = -0.37, P < 0.01 and r = -0.28, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Setting the standards for diabetes care: Hypertension

Setting the standards for diabetes care: Hypertension

Influence of proteinuria on vascular disease, blood pressure, and lipoproteins in insulin dependent diabetes mellitus.

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.

The Effect of Hypertension on Fetal Growth

To assess the effect of hypertension on fetal growth we studied all hypertensive patients who delivered at the University Hospital “Wilhelmina Gasthuis”, Amsterdam, over a five-year period. They were studied on a retrospective basis. Patients were excluded from this study if they had a multiple pregnancy or a hydatidiform mole. Out of 7454 women who delivered after 28 weeks gestation between 1975 and 1981, 716 nulliparae (N.P.) and 489 multiparae (M.P.) had a diastolic bloodpressure of ≥ 90 mm on at least two occasions. They were matched for age and parity with a normotensive control group, who delivered at our University Hospital in the same period. The Small-for-Gestational-Age (SGA) infant was designated as one whose birthweight fell below 5th percentile. Only the maximum diastolic bloodpressure level proved to have an association with the incidence of SGA infants. The influence of proteinuria appeared to be of minor importance with respect to fetal growth retardation when maximum diastolic bloodpressu...

The Effect of Hypertension on Fetal Growth

To assess the effect of hypertension on fetal growth we studied all hypertensive patients who delivered at the University Hospital “Wilhelmina Gasthuis”, Amsterdam, over a five-year period. They were studied on a retrospective basis. Patients were excluded from this study if they had a multiple pregnancy or a hydatidiform mole. Out of 7454 women who delivered after 28 weeks gestation between 1975 and 1981, 716 nulliparae (N.P.) and 489 multiparae (M.P.) had a diastolic bloodpressure of ≥ 90 mm on at least two occasions. They were matched for age and parity with a normotensive control group, who delivered at our University Hospital in the same period. The Small-for-Gestational-Age (SGA) infant was designated as one whose birthweight fell below 5th percentile. Only the maximum diastolic bloodpressure level proved to have an association with the incidence of SGA infants. The influence of proteinuria appeared to be of minor importance with respect to fetal growth retardation when maximum diastolic bloodpressu...