Orthostatic Proteinuria Research Articles

Mesangial Proliferative Nephritis in Man Is Associated with Increased Expression of the Cell Survival Factor, Bcl-2

Although most studies suggest that the hypercellularity in mesangial proliferative nephritis is due to increased cell proliferation, we hypothesized that it may also be due to increased expression of survival factors that may block their removal (apoptosis). We therefore studied the expression of apoptosis preventing/delaying the bcl-2 gene product in the glomerulus with various human glomerulonephritides. Immunohistochemistry for Bcl-2, proliferating cell associated protein (Ki-67) and α-smooth muscle actin (α-SMA) was performed on 55 biopsied kidney tissues: 6 cases of orthostatic proteinuria as a control (OP); 6 cases of diffuse proliferative lupus nephritis (WHO type IV, LN-MPGN); 24 cases of IgA nephropathy (IgA); 9 cases of minimal change nephrosis and 10 cases of idiopathic membranous nephropathy. The number of Ki-67-positive cells and the expression of α-SMA in the glomerulus were significantly higher in LN-MPGN and IgA. There was a significant positive correlation between glomerular Bcl-2 expression and glomerular cell proliferation evaluated by the number of Ki-67-positive cells (r = 0.605, p < 0.01) or glomerular α-SMA expression (r = 0.674, p < 0.01). Glomerular expression of Bcl-2 in IgA or LN-MPGN was significantly higher than that in OP (p < 0.01 and p < 0.05 vs. OP, respectively). The Bcl-2-positive cells were present in mesangial locations and demonstrated a perinuclear pattern. These results suggest that maintenance of glomerular hypercellularity in human glomerular diseases is partly due to the prevention of mesangial cell death via Bcl-2 expression.

Left renal vein entrapment syndrome in two girls with orthostatic proteinuria

Left renal vein entrapment was documented by bilateral ureteral catheterization and imaging studies as a cause of orthostatic proteinuria in two girls. Renal ultrasonography showed compression of the left renal vein between the aorta and the superior mesenteric artery (Nutcracker phenomenon). Abnormal collateral veins and high pressure gradients between the left renal vein and the inferior vena cava were found on left renal venography and pressure tracing, respectively. The left kidney was documented as the source of postural proteinuria by bilateral ureteral catheterization. Our observations suggest renal congestion due to left renal vein entrapment was the cause of orthostatic proteinuria.

Pathophysiological significance of plasma total renin and prorenin in patients with diabetes mellitus.

To seek the pathophysiologic significance of measuring the concentration of total renin instead of prorenin, we determined the plasma total renin concentration by immunoradiometric assay and correlated the results with various clinical features and laboratory parameters of diabetic complication in 108 patients with diabetes mellitus. The plasma prorenin concentration was estimated as the difference between the total and active renin concentrations. The plasma total renin and prorenin concentrations were high in patients with diabetes mellitus, in contrast to the active renin concentration which was slightly decreased. In addition, the plasma total renin and prorenin concentrations were higher in patients with diabetic complications than in patients without any complication. Multiple regression analysis showed that the presence of orthostatic hypotension, diabetic retinopathy, and proteinuria is significantly associated with the increased plasma total renin and prorenin concentrations. In addition, there was a significant positive correlation between the total renin and prorenin concentrations. These results suggest that both the plasma total renin concentration and the prorenin concentration are closely related to diabetic complications. Determination of the plasma total renin concentration by immunoradiometric assay as a substitute for prorenin could be a powerful tool in elucidating the mechanism for the increased plasma prorenin in diabetes mellitus.

Entrapment of left renal vein in children with orthostatic proteinuria

We found that patients with orthostatic protein-uria had entrapment of the left renal vein (LRV) by the aorta and superior mesenteric artery (SMA). Of 15 patients studied, ultrasonographic examination showed 13 cases of typical LRV entrapment with prestenotic dilatation, and 2 cases of mild LRV compression between the aorta and SMA. Intra-arterial digital subtraction angiography and monitoring of pull-back pressure from LRV to the inferior vena cava (IVC) were performed on 2 patients with 4+ proteinuria. Accumulation of contrast medium was seen with mild back-flow to the collateral veins, and pressure gradients between LRV and IVC were 4 mmHg and 8 mmHg, respectively. Eighty school-children formed a control group and were investigated ultrasonically. Nine showed typical LRV entrapment, among whom 3 had moderate to massive orthostatic proteinuria. The discovery of LRV entrapment in patients with orthostatic proteinuria gives definite evidence of LRV congestion and may be possibly a cause of massive protein secretion from the left kidney.

Mechanism of orthostatic proteinuria

Mechanism of orthostatic proteinuria

Contribution to the aetiopathogenesis of orthostatic proteinuria in children: relation to the upper calyx syndrome.

The authors discuss the correlations between the upper calyx syndrome and proteinuria. The syndrome was demonstrated in 33.6 per cent of all children with orthostatic proteinuria hospitalized at the Paediatric Clinic, Martin (Czechoslovakia) during 1978-1985. They consider the possible relations between these conditions that could be mediated by the activation of the renin/angiotensin II system. The direct stimulus of this system could rest in local ischaemization of parenchyma in the region of the proximal pole of the kidney or its partial passive congestion. They assume that these changes become more marked in the standing position and may cause proteinuria of orthostatic character. The inhibition of the renin/angiotensin II system may obviously lead to decreased proteinuria.

Proteinuria‐What Value is the Dipstick?

The value of the urinary dipstick in the assessment of proteinuria was investigated in a study correlating laboratory measurements of protein and albumin against the dipstick protein in the same samples of urine; 94 patients (100 admissions) were studied at the Royal Air Force Renal Unit, each patient collecting two 24-h urine samples. Along with each 24-h sample, 10-ml aliquots of urine were obtained at 3 designated times during the day for both ward dipstick testing and laboratory assay; + or more on the dipstick correlated with abnormal proteinuria (greater than or equal to 150 mg/24 h) in 88% of cases, whilst trace values straddled the level of significant proteinuria. Further differentiation of trace was possible by repeat testing during the day. The subsequent presence of a dipstick negative during that day correlated with normality in all but 5% of cases. In order to ensure detection of renal disease presenting as isolated orthostatic proteinuria, assay of the mid-morning sample is recommended.

Asymptomatic proteinuria. Benign disorder or harbinger of disease?

Proteinuria may be an indication of underlying disease or may be found in various physiologic states. Careful quantitation of urinary protein and thorough patient evaluation are necessary to determine if proteinuria is cause for concern. Transient and orthostatic proteinuria appear to be benign, but persistent proteinuria may be a manifestation of serious disease.

Studies of urine protein components of orthostatic proteinuria

Studies of urine protein components of orthostatic proteinuria

Orthostatic proteinuria and milk ingestion

An adolescent, contemplating a military career, was found to have orthostatic proteinuria. A thorough evaluation failed to reveal any renal abnormalities. He was tested on a milk-free diet at the request of the parents. The proteinuria cleared, but recurred on an initial open challenge; it did not recur subsequently on a blinded challenge. This experience suggests that patients with orthostatic proteinuria should be evaluated with an elimination diet trial.

Proteinuria in Sudanese children.

One thousand, eight hundred and forty-six apparently healthy nursery and school children living in the Khartoum area and belonging to different socio-economic classes were studied. Nine hundred and thirty-seven were boys, 909 girls. Their ages ranged from three to 16 years. N-multistix strips were used to test for proteinuria and haematuria, the former being also checked by the sulphosalicylic acid test. Children with proteinuria of 1+ or more were further investigated by examining their urinary sediment for abnormal deposits and by testing for orthostatic proteinuria using day and night specimens of urine with specific gravity of 1.018 or more. Children who had no proteins on orthostatic testing were rescreened for proteinuria 10-14 days after the initial screening. The prevalence rate for proteinuria was 7.2% with no significant difference between boys and girls. In both sexes the prevalence rate increased significantly with age but was not influenced by the socio-economic status. Of the children with proteinuria, haematuria occurred in 27% and abnormal urinary deposits in 14.8%. Orthostatic testing showed a negative result for proteins in 44%, orthostatic proteinuria in 40%, of whom a third had either abnormal urinary sediments or haematuria, and continuous proteinuria in 15.6% of whom the majority had abnormal deposits.

Evaluation of the Child with Asymptomatic Proteinuria

Asymptomatic proteinuria is defined as the discovery of proteinuria on a routine examination without evidence of clinical disease. The prevalence is dependent on the age and sex of the child, as well as the circumstances under which the testing is performed. In the majority of cases, patients have transient or orthostatic proteinuria. The physician can assure the patient and parents that the prognosis is excellent. However, appropriate long-term follow-up is essential. On the other hand, persistent proteinuria represents a spectrum from a benign disorder to a disease which can progress to end-stage renal failure.

Evaluation of the Child with Asymptomatic Proteinuria

Asymptomatic proteinuria is defined as the discovery of proteinuria on a routine examination without evidence of clinical disease. The prevalence is dependent on the age and sex of the child, as well as the circumstances under which the testing is performed. In the majority of cases, patients have transient or orthostatic proteinuria. The physician can assure the patient and parents that the prognosis is excellent. However, appropriate long-term follow-up is essential. On the other hand, persistent proteinuria represents a spectrum from a benign disorder to a disease which can progress to end-stage renal failure.

X-ray changes in the kidneys of children with orthostatic proteinuria.

In 38 patients with orthostatic proteinuria (O.P.) and in 31 children of the control group (C) roentgenograms of excretory urography have been compared, made in the standing erect and in the lying down posture. In children with O.P. significantly more frequent and more expressive ptosis of the kidneys during orthostasis was found than in the controls. In children with O.P. disturbed urine outflow was found in 36.8%, while in children of the control group only in 3.2%. On the basis of the results obtained relations between haemodynamic changes in ptosis of the kidneys, disturbed urine outflow and the origin of O.P. are analysed.

Fixed and reproducible orthostatic proteinuria: results of a 20-year follow-up study.

A 20-year follow-up evaluation of young men with fixed and reproducible orthostatic proteinuria showed no evidence of progressive renal disease. Follow-up information was obtained on 43 of the original 64 patients and detailed information was secured on 36. All had normal renal function and only six patients continued to show qualitative proteinuria. The prevalence of hypertension found was similar to that of a comparably aged group of the general population. The 20-year prognosis of patients with fixed and reproducible orthostatic proteinuria is excellent.

Renal biopsy findings in orthostatic proteinuria.

Percutaneous renal biopsy was performed on 15 patients with orthostatic proteinuria and 6 control subjects without proteinuria in order to investigate possible renal alterations. The light-microscopic findings were either normal or showed slight mesangial proliferation in the orthostatic group but were normal in the control subjects, while the immunofluorescence-microscopic study revealed mesangial, capillary or arteriolar deposits of complement C3 and/or immunoglobulins in 10 out of 12 cases with orthostatic proteinuria; complement C3 was seen in only one control subject. The electron-microscopic findings were similar in the two groups, showing slight subepithelial, intramembranous and mesangial alterations. Focal loss of the epithelial foot processes was seen in only one case with orthostatic proteinuria. It is concluded that there are no histological, electron microscopical or immunohistochemical alterations specific for orthostatic proteinuria. A finding of complement in the glomeruli in about half and of immunoglobulin in some of the patients with orthostatic proteinuria is in favour of an association to present or previous glomerulonephritis.

Prevalence and causes of proteinuria in 20-year-old Finnish men.

The prevalence and causes of proteinuria were studied in a cohort of 36147 men aged 20 (born in 1956). Proteinuria was found in 139 men (0.4%) at the initial screening or examination. Further investigations reduced the number of proteinuria cases to 72 (0.2%). Persistent proteinuria was demonstrated in 46 men (0.13% of the series) and orthostatic proteinuria in 26 (0.07%). Urography revealed anomalies in 18 of 104 cases. Elevated blood pressure and reduced glomerular filtration rate were observed in a few men, mainly from the group with persistent proteinuria. Renal biopsy was performed in 61 cases--38 with persistent proteinuria, 12 with orthostatic proteinuria and 11 without proteinuria at the time of examination. Light microscopy gave normal findings or showed only slight mesangial or focal glomerulonephritis in the great majority of cases. Membranous, mesangiocapillary or chronic proliferative glomerulonephritis was present in one-fourth of the men with persistent proteinuria. This was the only group with such lesions.

Long-term outcome and clinical significance of orthostatic proteinuria.

Long-term outcome and clinical significance of orthostatic proteinuria.

Enzymuria as a Marker of Renal Injury and Disease

We concur with the comments made by Dr. Kunin and colleagues in their article on N-acetyl-β-glucosaminidase (NAG) as a marker of renal injury (Pediatrics 62:751, 1978). Despite a correlation between enzymuria and proteinuria in Figure 6, we feel that both proteinuria and enzymuria reflect the underlying renal damage. In addition to NAG, we also studied three other urinary lysosomal acidic hydrolases—β-galactosidase, α-fucosidase, and arylsulfatase—in children with renal disease.1 In three children with orthostatic proteinuria, despite increased proteinuria in upright posture, enzymuria remained normal both in recumbent and upright posture.1

Contribution to the etiopathogenesis of orthostatic proteinuria in children.

The results of sequential scintigraphy of the kidneys of 22 children with orthostatic proteinuria and of 25 patients with nephritis or nephrotic syndrome, respectively, have been evaluated. At particular time intervals significant differences have been found between the two groups. On the basis of the visual method of evaluation of scintiscans and by bilateral comparison the authors conclude that in children with orthostatic proteinuria the frequency of asymmetry of the kidneys was significantly higher. These changes were most likely due to spasms or other disturbances of the function of excretory urinary passages in the calyx-pelvis system as responses to unfavourable emotional inpulses (intravenous application of the substance, etc.) and to the sitting position during the examination.