Postural Proteinuria Research Articles

Left renal vein entrapment in postural proteinuria: the diagnostic utility of the aortomesenteric angle.

Nutcracker syndrome related to the left kidney vein compression is a cause of orthostatic proteinuria during childhood. Some studies have shown that the ratios between maximum velocities and anterior-posterior diameters of hilar and aortomesenteric segments of the left kidney vein between upright and supine positions must be more than 4 in order to make a Nutcracker syndrome diagnosis. Our aim was to investigate whether the use of a decrease in aortomesenteric angle between upright and supine positions in the presence of isolated orthostatic proteinuria can be a criterion for the diagnosis of Nutcracker syndrome. Relevant patient information, which included demographic data, clinical examination findings, laboratory data, urinary system ultrasound, and kidney color flow Doppler ultrasound results, were prospectively collected. Thirty-nine pediatric patients with orthostatic proteinuria were included in the study. Left kidney vein compression findings were demonstrated in 31 patients. The ratio of maximum velocities of hilar and aortomesenteric segments of the left kidney vein between upright and supine positions was above 4 in only 7 of our patients. Ratio of aortomesenteric angle between upright and supine positions was significantly decreased for patients with left kidney vein compression findings. Conclusion: The use of a decrease in the ratio of aortomesenteric angle between upright and supine positions in the presence of orthostatic proteinuria, instead of the ratios for maximum velocities and anterior-posterior diameters of hilar and aortomesenteric segments, can be more helpful for the diagnosis of Nutcracker syndrome in the differential diagnosis of orthostatic proteinuria. What is Known: •Proteinuria may be a sign of an impending kidney disease •Nutcracker syndrome is a cause of orthostatic proteinuria. What is New: •Ratio of aortomesenteric angle between upright and supine positions > 0.6 can be used for Nutcracker syndrome diagnosis.

Proteinuria

Key Points Proteinuria on routine screening of children without symptoms most often is either orthostatic or transient, not pathological. Orthostatic (postural) proteinuria is most common. Transient proteinuria can result from stressors such as fever or vigorous exercise. Persistent (fixed) proteinuria can be asymptomatic, signaling underlying glomerular or tubular renal disease.

A Case of Orthostatic Proteinuria Progressed to Persistent Proteinuria Associated with Renal Pathology

Orthostatic or postural proteinuria is the most common cause of asymptomatic proteinuria in children. As orthostatic proteinuria (OP) is a benign disease with relatively good prognosis, it has no specific management, and patients only need to be observed. However, if OP shows a persistently high level of proteinuria, in theory, glomerular changes can occur. An 11-year-old girl was referred to the hospital due to asymptomatic proteinuria and was diagnosed as having OP based on the results of clinical and laboratory examinations, urinalysis, and protein/creatinine (TP/Cr) ratio at both supine and erect positions. During follow-up observation, the 24-hour TP/Cr ratio was persistently higher than 1.5 mg/mg for 2 years. We performed renal biopsy, which showed mesangial proliferative glomerular lesions with focal effacement of the podocyte foot processes, but without immune depositions. OP can be accompanied by glomerular lesions if moderate to severe proteinuria persists. Key words: Proteinuria; Glomerulonephritis; Child; Orthostatic proteinuria

Should screening of renal markers be recommended in a working population?

It is debated whether the general population should be screened for kidney disease. This study evaluated whether screening of albuminuria and estimated glomerular filtration rate (eGFR) in a working population should be recommended to detect subjects with chronic kidney disease. The unreferred renal insufficiency study is a cross-sectional study in 1,398 workers aged 17-65. Markers of cardiovascular and renal disease were measured. Cardiovascular risk (CVR) was defined by hypertension (n = 416), diabetes (n = 45), dyslipidemia (n = 159) and/or history of a cardiovascular event (n = 10). In our population, 5 % of the workers had microalbuminuria, 0.5 % had macroalbuminuria and <0.1 % had eGFR <60 ml/min/1.73 m(2). All workers with an eGFR <60 ml/min/1.73 m(2) and/or macroalbuminuria (8/8) had at least one CVR factor, whereas this was the case in only half of workers with microalbuminuria (36/73, p = 0.007). In workers without CVR factors, the presence of microalbuminuria was associated with low body mass index (BMI, p < 0.001) or physiochemical exposure risk (p < 0.001). Screening of renal markers in a working population, identified only a few subjects with an eGFR <60 ml/min/1.73 m(2) or macroalbuminuria. Although microalbuminuria was more prevalent, it might not necessarily indicate kidney disease, as it may have a completely different meanings depending of the phenotype of the screened subjects. Besides underlying CVR factors, microalbuminuria was also associated with low BMI in absence of any risk factor, suggesting presence of benign postural proteinuria. In addition, microalbuminuria also seemed to be related to physicochemical exposure. In view of the impossibility to further analyze this finding in the present study, the meaning of this observation needs to be further investigated.

Nutcracker phenomenon and idiopathic IgA nephropathy.

Sir, Entrapment of the left renal vein between the aorta and the superior mesenteric artery is a documented cause of both postural proteinuria as well as intermittent gross haematuria associated with left flank pain. Idiopathic IgA nephropathy typically presents with recurrent episodes of gross haematuria, usually following an acute febrile illness. Rarely, the disease presents as microscopic haematuria and usually mild proteinuria. We present the first case of postural proteinuria caused by left renal vein entrapment and recurrent gross haematuria caused by an IgA nephropathy. In an 11-year-old boy with postural proteinuria, renal ultrasonic Doppler disclosed left renal vein entrapment: the anteroposterior diameter at the hilar portion divided by that at the aortomesenteric portion was 13.3 (reference ≤ 4.0) and the peak flow velocity at the aortomesenteric portion divided by that at the hilar portion 15.1 (reference ≤ 4.0). Two years later, three episodes of acute febrile diarrhoea were followed by gross haematuria that was not associated with flank pain. The kidney biopsy showed mild diffuse mesangial proliferation and matrix expansion. The diagnosis of IgA nephropathy was made on immunofluorescence microscopy, which demonstrated isolated prominent globular deposits of IgA, C3 and IgG in the mesangium. The link between left renal vein entrapment and postural proteinuria is well documented. Furthermore, both left renal vein entrapment and IgA nephropathy are recognized causes of recurrent gross haematuria. There are five reported patients affected with both left renal vein entrapment and idiopathic IgA nephropathy [1–4]. A 12-year-old German girl with microscopic haematuria was found to have left renal vein entrapment and mesangial deposits of IgA [1]. Similarly, left renal vein entrapment and mesangial deposits of IgA were reported in a 9-year-old Korean girl with isolated microscopic haematuria and recurrent gross haematuria [2] and in a 25-year old Taiwanese woman with recurrent gross haematuria and left flank pain [3]. Left renal vein entrapment and IgA nephropathy were also disclosed in a 20-year-old woman and in a 22-year-old Japanese man, who, in the context of a pharyngitis, developed gross haematuria and a tendency to microscopic haematuria with persisting proteinuria [4]. In addition, left renal vein entrapment was disclosed in two Korean children a 13-year-old Korean girl with Henoch–Schonlein syndrome and IgA nephropathy [5]. Finally, a 10-year-old Korean boy with a clinically characteristic and rapidly resolving form of Henoch–Schonlein syndrome followed by microscopic haematuria persisting for 26 months was found to have left renal vein entrapment; haematuria subsided in accordance with radiological improvement of renal vein entrapment [6]. Our patient is the first case with concurrent existence of postural proteinuria caused by left renal vein entrapment and recurrent gross haematuria caused by an idiopathic IgA nephropathy. Renal venous congestion may induce both proteinuria and haematuria, which have been implicated as a cause of renal damage. So, a causal relationship between left renal vein entrapment and IgA nephropathy cannot be ruled out. Further investigations are necessary to detect this correlation.

Renal vein obstruction and orthostatic proteinuria: a review

The cause of orthostatic proteinuria is not clear but may often relate to obstruction of the left renal vein in the fork between the aorta and the superior mesenteric artery (=renal nutcracker). However, reports dealing with proteinuria only marginally refer to this possible cause of orthostatic proteinuria. We analysed the corresponding literature. Five reports addressed the frequency of renal nutcracker in 229 subjects with orthostatic proteinuria. Their age ranged between 5.2 and 17 years (female-to-male ratio: 0.96:1.00). Imaging studies demonstrated renal nutcracker in 156 (68%) subjects. Renal nutcracker was also demonstrated in 9 anecdotal reports for a total of 53 subjects with postural proteinuria. Very recently, 13 Italian subjects with orthostatic proteinuria associated with renal nutcracker were reassessed 6 years after the initial diagnosis: in nine subjects, both orthostatic proteinuria and renal nutcracker had disappeared; in three, both orthostatic proteinuria and renal nutcracker had persisted; and in one, orthostatic proteinuria had persisted unassociated with renal nutcracker. These data provide substantial support for renal nutcracker as a common cause of orthostatic proteinuria.

Postural Proteinuria Associated With Left Renal Vein Entrapment: A Follow-up Evaluation

Imaging studies show entrapment of the left renal vein in the fork between the aorta and proximal superior mesenteric artery in most cases of isolated postural proteinuria. Therefore, it has been postulated that partial obstruction to the flow in the left renal vein in the upright position is a cause of this form of proteinuria. In a girl with isolated postural proteinuria, kidney ultrasonic imaging and Doppler flow scanning showed left renal vein entrapment. Seven years later, a new evaluation showed resolution of both postural proteinuria and left renal vein entrapment. The longitudinal observation provides substantial additional support for entrapment of the left renal vein by the aorta and superior mesenteric artery as a cause of isolated postural proteinuria.

Body mass index modulates postural proteinuria

Dear Sir, In contrast to constant proteinuria, postural proteinuria has been generally regarded as a benign condition [1–4]. However, anecdotal observations suggest that postural proteinuria might sometimes reflect incipient kidney disease [5, 6]. To further address this controversy we recently reassessed 15 subjects with fixed and reproducible postural proteinuria two or more years after the initial diagnosis. After breakfast and after starting an appropriate water load, the subjects came to the clinic. They had been advised to bring along a portion of the first morning urine (‘‘recumbent’’) for determination of the total protein-to-creatinine ratio (reference value: B30 mg/mmol) [7]. The second morning urine sample was collected for urinary sediment analysis and blood was taken for determination of creatinine. Urinary total protein-to-creatinine ratio was also determined with the subjects in a nonrecumbent position for C3 h. Finally height, body weight, and sitting blood pressure (reference: systolic and diastolic blood pressure \90th centile for gender, age, and height in subjects less than 18 years of age and \140/90 mmHg in the remaining subjects) were recorded and a complete physical examination performed. Body mass index was calculated as the body weight in kilograms divided by squared height in meters [8, 9] and the glomerular filtration rate (reference value: C90 ml/[min. 1.73 m]) estimated from height and circulating creatinine using the ‘‘height to creatinine equations’’ [10]. Since body mass index (in kg/m) varies with age, this parameter was also plotted on the body mass index for age and gender charts and expressed as centile adjusted for age and gender [8]. Descriptive statistics are presented as numbers for qualitative data, and as median and interquartile range (which extends from the value at the 25th to that at the 75th centile and includes half of the data points) for quantitative data. v-test (qualitative data) and Mann-Whitney-Wilcoxon test for independent samples (quantitative data) were used for analysis. Statistical significance was set at the 0.05 level. In the recently reevaluated subjects, whose age ranged from 10 to 24 years, the diagnosis of postural proteinuria had been made 2.3–15 years earlier. Physical examination, blood pressure, glomerular filtration rate, urinalysis, and recumbent urinary total proteinto-creatinine ratio were normal in the subjects. Nonrecumbent urinary total protein-to-creatinine ratio G. Milani E. F. Fossali (&) Clinica Pediatrica De Marchi, Foundation IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Commenda 9, 20122 Milan, Italy e-mail: mimmofox2000@yahoo.it

Left renal vein entrapment: a frequent feature in children with postural proteinuria

In most Asian subjects with postural proteinuria, ultrasonic imaging and Doppler flow scanning disclose entrapment of the left renal vein in the fork between the aorta and the superior mesenteric artery. Little information is available on the possible occurrence of left venal rein entrapment in European subjects with postural proteinuria. Renal ultrasound with Doppler flow imaging was therefore performed on 24 Italian or Swiss patients with postural proteinuria (14 girls and ten boys, aged between 5.2 years and 16 years). Signs of aorto-mesenteric left renal vein entrapment were noted in 18 of the 24 subjects. In conclusion, aorto-mesenteric left renal vein entrapment is common also among European subjects with postural proteinuria.

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.

Reversed – Phase High – Performance Liquid Chromatography for Analysis of Urinary Proteins: Diagnostic Significance of &lt;i&gt;α&lt;/i&gt;&lt;sub&gt;1&lt;/sub&gt;&lt;i&gt;-&lt;/i&gt;Acid Glycoprotein

In order to analyze urinary proteins from patients with various renal diseases, a reversed-phase high-performance liquid chromatography with IPG PACK ODS column packed with polyporous glass was employed. The peak areas of alpha 1-acid glycoprotein (alpha 1-AGP), beta 2-microglobulin (beta 2-MG) and albumin were measured by a chromato-integrator. The alpha 1-AGP/albumin ratio was regarded as the marker of glomerular damage, while the beta 2-MG/albumin ratio indicated tubular dysfunction. As a result, the alpha 1-AGP/albumin ratio in the urine from patients with either various glomerulonephritis (GN) or idiopathic nephrotic syndrome was significantly higher than that from either patients with postural proteinuria or healthy children. However, the beta 2-MG/albumin ratio in the urine from patients with GN was the same level as controls. The beta 2-MG/albumin ratio was elevated only in urine from patients with tubular dysfunctions. These data suggest that the urinary alpha 1-AGP/albumin ratio could be a beneficial indicator in locating patients with GN from among children with asymptomatic proteinuria.

Studies of the analysis of urinary proteins from children with renal diseases by reversed-phase high performance liquid chromatography

In order to analyze urinary proteins from patients with various renal diseases, a reversed-phase high performance liquid chromatography (HPLC) with IPG PACK ODS column packed with polyporous glass was used. The reproducibility of standard proteins was good. The results by this method correlated well with those by radioimmunoassay or laser nephelometry, precolumn procedure needed the centrifugation only. The reversed-phase HPLC was superior to the other HPLC methods in the analysis of urinary proteins for its simplicity and high sensitivity. The peaks of both alpha 1-acid glycoprotein (alpha 1-AGP) and human serum albumin (HSA) in the chromatogram was regarded as the marker of renal damage. Urinary alpha 1-AGP/HSA ratio was calculated after measuring these two peak areas. As a result, it was significantly higher in the urine from patients with various glomerulonephritis (GN) than in those from healthy children. In the patients with postural proteinuria, it was the same level as that in healthy children. These date suggest that the urinary alpha 1-AGP/HSA ratio would be a beneficial indicator to find out the patients with GN from among children with proteinuria. Furthermore, it seems that this method is suitable for use in routine screening of renal diseases for its simplicity and speed.

Quantitative determination of urinary protein components of children with postural proteinuria.

Twenty-one protein components were measured in urine specimens from 12 subjects with postural proteinuria in the recumbent posture and after a period of upright lordotic posture. The lordotic posture produced an increased urinary excretion of total protein and 19 protein components, particularly of albumin, IgG globulin, and transferrin (128, 68, and 167-fold, respectively). However, 90 min after the lordotic posture, most of the protein components returned to initial values, whereas albumin, IgG globulin, and transferrin remained high. beta 2-Microglobulin, retinol binding protein, and lysozyme showed the smallest increases after the lordotic posture. These findings suggest that proteinuria occurring after the lordotic posture may be characterized by an increased glomerular permeability.

SELECTIVITY AS A CLUE TO DIAGNOSIS OF POSTURAL PROTEINURIA

In 14 patients with fixed and reproducible postural proteinuria and 14 patients with histologically proven glomerulonephritis, the selectivity of proteinuria was measured separately in the day and night urine collections. The selectivity of proteinuria in the urine collected in recumbency was lower in patients with glomerulonephritis than in patients with postural proteinuria. All patients with postural proteinuria showed an increment of the selectivity from day to night of at least 13°, whereas the maximum increment in patients with glomerulonephritis was 5°. The changes in selectivity from day to night in patients with postural proteinuria and patients with glomerulonephritis were significantly different and seem to be a useful discriminatory test.

Postural proteinuria and lipoid nephrosis of 58 years' duration

Postural proteinuria and lipoid nephrosis of 58 years' duration

PARTICIPATION OF FOCAL INFECTION COEXISTING WITH FOOD SENSITIVITY IN THE ETIOLOGY OF POSTURAL PROTEINURIA

In the previous papers, Matsumura et al. reported that food sensitivity play an important role on the etiology of postural proteinuria (PP). Namely, PP was obviously induced by trial ingestion of allergenic foods such as milk, egg, soybean, pork, redbean and/ or mackerel, and clearly removed by their elimination. Avoidance also made the accompanying symtoms improved. PP in this series dealt with the proteinuria induced by the erect lordotic posture. In other words, our subjects should strictly be called lordotic proteinuria (LP).In this paper, 9 cases of LP, aged 5 to 13 yrs. and consisted of 6 girls and 3 boys, were reported, in which LP still persisted even after eliminating a few or more suspected foods and finally disappeared or markedly improved by eradicating infectious foci such as inflammed tonsils and adenoid as well as decayed teeth. The periods necessary for inducing improvement were 2/3- 12 (average 3.9) months after eradication. The infectious foci removed were as follow carious teeth in 1 case ; tonsils in 3; carious teeth and tonsils in 4 ; tonsils and adenoid in one. On light microscopy of 2 renal biopsy specimens, one showed minimal abnormalities including a focal slight increase in mesangial cells, and another a diffuse slight mesangial proliferation. In the latter, immunofluorescent study revealed deposits of IgM in mesangial regions and walls of vasa afferentia as well as along the capillary loops. Deposits of IgG and β1C were also seen along the peripheral capillary walls of glomeruli. On the electron microscopic examination, focal foot process fusions and so on were observed in both cases.From these findings it might be suggested that focal infection coexisting with food sensitivity play an important role in the pathogenesis of postural proteinuria.

Albumin and creatinine clearances in renal disease.

1. The ratio of albumin clearance to creatinine clearance (CA/CC) was determined on 129 occasions in forty patients with a wide variety of renal diseases, both 24 h collections of urine and random mid-morning samples being used. The clearance ratios derived from 24 h urine (24 h CA/CC) and random urine (R CA/CC) were compared with random urine protein concentration, 24 h urine protein excretion and 24 h urine albumin excretion. 2. From these measurements 24 h CA/CC could only be predicted accurately by R CA/CC, particularly when patients with postural proteinuria were excluded. 3. The diurnal variation of CA/CC was investigated in twelve patients with renal disease. The individual values for CA/CC obtained throughout the day were within the limits of prediction of 24 h CA/CC already established. The diurnal variation of CA/CC was considerably less than that of CA or CC alone and also less than that of the rates of protein and albumin excretion. 4. It is suggested that CA/CC is the best readily available measure of ‘glomerular leakiness’ and examples are given of its clinical value. In patients with renal disease 24 h CA/CC could be predicted, in this study, from the clearance ratio based on simultaneous random urine and blood samples.

Postural proteinuria in pregnancy

A 21-yr-old woman showed an extremely variable proteinuria in the last trimester of her first pregnancy. The loss of protein proved to be directly caused by the supine position. The amount of protein excreted during 1 h in the supine position was equivalent to a 24-h protein excretion of 18 g. In contrast, the loss of protein in other positions was very low. The patient had no hypertension or other toxemic symptoms and the existence of a hypotensive syndrome could be ruled out.

Glomerular permeability to high molecular weight dextrans in acute ischaemic renal failure and postural proteinuria.

1. Renal permeability to dextran of a molecular weight range approximating to that of the plasma proteins has been studied in six patients with acute ischaemic renal failure, four patients with postural proteinuria and six healthy subjects. 2. Results are expressed in terms of dextran selectivity indices which relate the clearance of dextran to its molecular weight. Indices of dextran selectivity were found to be high in acute ischaemic renal failure, postural proteinuria and in normal subjects. Comparable indices of plasma protein selectivity in these groups were low. 3. It is suggested that in postural proteinuria and acute ischaemic renal failure the proteinuria is not glomerular in origin, and that in these conditions macromolecules are filtered quite normally and urinary protein arises from a post glomerular source characterized by a lack of selectivity.

Glomerular ultrastructure and function in postural proteinuria.

Electron microscopic studies of glomeruli and determination of protein clearances were made in seven patients presenting with postural proteinuria, with no evidence of established renal disease. In all cases renal biopsies were taken while the patient had proteinuria; in three another biopsy was obtained in the absence of proteinuria. Individual protein clearances of five serum proteins of widely differing molecular weights were estimated by immunological methods. On electron microscopy focal abnormalities were seen in all glomeruli. ‘Ballooning’ of epithelial cell cytoplasm with patchy fusion of foot processes and increased numbers of Folli bodies were noted. The basement membrane appeared normal in all cases embedded in Araldite. The changes described in epithelial cells are common to most conditions giving rise to proteinuria. There was no significant ultrastructural difference between biopsies taken in the presence of and in the absence of proteinuria. Results of protein clearance studies show that the proteinuria is highly unselective in these patients, and is similar to the excretion pattern found in normal individuals, contrasting with proteinuria in minimal lesion glomerulonephritis which is highly selective. This suggests that in spite of some morphological similarity to minimal lesion glomerulonephritis, postural proteinuria is in fact unrelated to this condition and may be a physiological variant of normal function. This view cannot be established with certainty without long-term follow up and serial examinations of biopsy material from such patients.