• Sign Up

Use coupon code EXTENDEDHOLIDAY2020 at checkout for 20% off

Orthostatic Proteinuria


Orthostatic Proteinuria

Article Author:
Curtis Ingold
Article Editor:
Harshil Bhatt
Updated:
12/1/2020 10:09:56 PM
For CME on this topic:
Orthostatic Proteinuria CME
PubMed Link:
Orthostatic Proteinuria

Introduction

Orthostatic proteinuria, also known as postural proteinuria, is a condition where an abnormally large amount of protein is excreted in the urine when the patient is in an upright position and normal protein excretion in the supine position.[1] It affects approximately 2 to 5% of adolescents and is uncommon after 30 years of age.[2] Orthostatic proteinuria is a benign condition.[3] 

Proposed mechanisms include that it is a normal variant, there is a subtle glomerular abnormality, it is an exaggerated hemodynamic response, and it is due to a left renal vein entrapment.[4][5][6][7] This article will discuss the etiology, epidemiology, pathophysiology, evaluation, and management of orthostatic proteinuria in greater detail.

Etiology

There are several proposed mechanisms for the cause of orthostatic proteinuria:

  • Normal variant
  • Subtle glomerular abnormality
  • Exaggerated hemodynamic response
  • Left renal vein entrapment

Mahurkar et al. supported the normal variant mechanism. In a study with 120 healthy male volunteers that showed the difference in proteinuria with laying down versus standing up. The study participants were from 11 to 36 years of age. Urine was collected after lying supine for one hour and then again after patients were standing for one hour with only gentle walking allowed. Proteinuria was measured in both urine samples and was higher in 20% of the patients after standing for an hour, compared to the other 80%, which had a decrease in protein excretion with a corresponding reduction in creatinine clearance. The authors concluded that there might be a broader distribution curve for standing protein excretion.[4]

Subtle glomerular abnormalities in the setting of abnormal glomerular hemodynamics may contribute to protein loss in patients with orthostatic proteinuria. A study by Sinniah et al. compared 55 young, healthy men in Singapore via renal biopsy. The subjects had either persistent proteinuria or orthostatic proteinuria. Men with orthostatic proteinuria showed subtle glomerular abnormalities that the researchers thought to be contributing to the proteinuria.[5] Additionally, another study by Robinson et al. looked at 56 healthy men between the ages of 17 and 24 years with asymptomatic orthostatic proteinuria. They obtained renal biopsies, and 43% showed thickening of the glomerular capillary wall that was minimal to moderate. The authors concluded that subtle glomerular abnormalities might contribute to orthostatic proteinuria.[8]

An exaggerated hemodynamic response could cause orthostatic proteinuria by increased efferent arteriolar resistance, likely from the action of angiotensin II. An article by Vehaskari critiqued this mechanism, suggesting that orthostatic proteinuria is multifactorial and that the exaggerated hemodynamic response mechanism is probably only a contributing factor.[6] The renin-angiotensin-aldosterone system (RAAS) is a component of renal pathogenesis.[9]

Left renal vein entrapment showed to be common in patients with orthostatic proteinuria.[7] There is a hypothesis that partial obstruction of the left renal vein in the upright position causes orthostatic proteinuria by altering glomerular microcirculation and increasing protein filtration.[10]

Epidemiology

Orthostatic proteinuria is the most frequent cause of isolated proteinuria in adolescents and children. It affects approximately 2 to 5% of adolescents and is uncommon after 30 years of age.[2] Orthostatic proteinuria is more common in boys.[11] There have been conflicting results about whether children with obesity or children that are underweight have a higher tendency for orthostatic proteinuria.[11][12]

Histopathology

Robinson et al. evaluated renal biopsies in patients with orthostatic proteinuria and noted these findings:[8]

  • Eosinophilic granules within capsular space in 67% of specimens
  • Minimal to moderate thickening of the glomerular capillary wall in 43% of specimens
  • Glomerular hypercellularity in 41% of specimens
  • Focal capillary dilatation in 22% of specimens

History and Physical

A thorough history and physical exam should be obtained from the patient with the assistance of their guardian if needed. Positive family history or past medical disease positive for the renal disease may suggest a pathology other than orthostatic proteinuria.

Evaluation

In patients with suspected orthostatic proteinuria, the clinician should obtain a urinalysis from the first-morning void sample. If the first-morning urine has normal urinary protein, then these patients do not require further investigations for renal disease.[11] Normal urinary protein excretion is usually less than 150 mg/day. There is no indication for renal biopsy in asymptomatic isolated orthostatic proteinuria but should be a consideration if the patient presents with signs of vasculitis, active urinary sediments, hypertension, persistent or gross hematuria, renal insufficiency, or hypocomplementemia.[3] A clinically significant renal disease is more likely when proteinuria presents with hematuria.[13]

A urine protein-to-creatinine ration can also help with the diagnosis. A normal urine protein/creatinine ratio in a recumbent position (< 0.2mg/mg creatinine) with a high ratio in samples collected in standing position establishes the diagnosis.

Treatment / Management

There are no formal guidelines for monitoring in patients with orthostatic proteinuria. However, the recommendation has been for annual follow-ups. Diet and physical activity should not be restricted.[3]

Surgical intervention, including stenting for left renal vein entrapment, is not recommended to treat asymptomatic orthostatic proteinuria.[14] Additionally, clinicians should not use angiotensin-converting-enzyme (ACE) inhibitors and other medications to treat asymptomatic isolated orthostatic proteinuria.[15]

Differential Diagnosis

Persistent proteinuria is a differential diagnosis that must be kept in mind. Other causes of proteinuria in children include transient proteinuria and persistent proteinurias such as Alport syndrome, diabetes mellitus, glomerulopathy, infections, malignancies, toxins, acute tubular necrosis, polycystic kidney disease, and proximal renal tubular acidosis.[3]

Prognosis

Orthostatic proteinuria is a benign condition. A 20-year follow-up by Springberg et al. in patients with orthostatic proteinuria did not find evidence for progressive renal disease.[16]

In the follow-up evaluation by Springberg et al., they evaluated 64 patients that Robinson et al. had studied 20 years prior.[8][16] They obtained detailed information from 36 of the original 64 patients, and only six patients demonstrated qualitative proteinuria. None of the 64 patients had to undergo kidney transplantation or dialysis in the Veterans Administration hospital system.[16]

Complications

There is no evidence of complications from orthostatic proteinuria.[16]

Deterrence and Patient Education

Patient education is an integral aspect of managing orthostatic proteinuria. While proteinuria is not normal, a patient should receive education regarding the clinical significance of this disease.

Enhancing Healthcare Team Outcomes

Orthostatic proteinuria is a benign and self-limiting disease seen mostly in children and young adults. There are no formal guidelines for monitoring, but several nephrologists have recommended at least yearly monitoring.[3][11] The management of orthostatic proteinuria can be optimized with an interprofessional approach. Pediatricians and other healthcare providers are vital to diagnosing orthostatic proteinuria. Patients can be referred to a nephrologist if the primary provider is unsure of an accurate diagnosis. Nursing staff can help by obtaining proper urine specimens. Pharmacists can contribute by reinforcing to patients that asymptomatic isolated orthostatic proteinuria does not require the use of medications. In conclusion, orthostatic proteinuria is a benign condition that does not require extensive testing. [Level 3]


References

[1] Vehaskari VM, Orthostatic proteinuria. Archives of disease in childhood. 1982 Oct;     [PubMed PMID: 7138061]
[2] Uehara K,Tominaga N,Shibagaki Y, Adult orthostatic proteinuria. Clinical kidney journal. 2014 Jun;     [PubMed PMID: 25852903]
[3] Leung AK,Wong AH,Barg SS, Proteinuria in Children: Evaluation and Differential Diagnosis. American family physician. 2017 Feb 15;     [PubMed PMID: 28290633]
[4] Mahurkar SD,Dunea G,Pillay VK,Levine H,Gandhi V, Relationship of posture and age to urinary protein excretion. British medical journal. 1975 Mar 29;     [PubMed PMID: 804953]
[5] Sinniah R,Law CH,Pwee HS, Glomerular lesions in patients with asymptomatic persistent andorthostatic proteinuria discovered on routine medical examination. Clinical nephrology. 1977 Jan;     [PubMed PMID: 318947]
[6] Vehaskari VM, Mechanism of orthostatic proteinuria. Pediatric nephrology (Berlin, Germany). 1990 Jul;     [PubMed PMID: 2206899]
[7] Ragazzi M,Milani G,Edefonti A,Burdick L,Bianchetti MG,Fossali EF, Left renal vein entrapment: a frequent feature in children with postural proteinuria. Pediatric nephrology (Berlin, Germany). 2008 Oct;     [PubMed PMID: 18607641]
[8] ROBINSON RR,GLOVER SN,PHILLIPPI PJ,LECOCQ FR,LANGELIER PR, Fixed and reproducible orthostatic proteinuria. I. Light microscopic studies of the kidney. The American journal of pathology. 1961 Sep;     [PubMed PMID: 13742344]
[9] Pramod S,Mustafa BO,Khitan ZJ, Can Aliskiren     [PubMed PMID: 30912232]
[10] Milani GP,Mazzoni MB,Burdick L,Bianchetti MG,Fossali EF, Postural proteinuria associated with left renal vein entrapment: a follow-up evaluation. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2010 Jun;     [PubMed PMID: 20430499]
[11] Brandt JR,Jacobs A,Raissy HH,Kelly FM,Staples AO,Kaufman E,Wong CS, Orthostatic proteinuria and the spectrum of diurnal variability of urinary protein excretion in healthy children. Pediatric nephrology (Berlin, Germany). 2010 Jun;     [PubMed PMID: 20165888]
[12] Arslan Z,Koyun M,Erengin H,AkbaĊŸ H,Aksoy GK,Çomak E,Akman S, Orthostatic proteinuria: an overestimated phenomenon? Pediatric nephrology (Berlin, Germany). 2020 May 11;     [PubMed PMID: 32394189]
[13] Leung AK,Wong AH, Proteinuria in children. American family physician. 2010 Sep 15;     [PubMed PMID: 20842993]
[14] Milani G,Fossali EF,Bianchetti MG, Re: Wang et al.: Diagnosis and surgical treatment of nutcracker syndrome: a single-center experience. (Urology 2009;73:871-876). Urology. 2009 Aug;     [PubMed PMID: 19646636]
[15] Mazzoni MB,Kottanatu L,Simonetti GD,Ragazzi M,Bianchetti MG,Fossali EF,Milani GP, Renal vein obstruction and orthostatic proteinuria: a review. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011 Feb;     [PubMed PMID: 20656752]
[16] Springberg PD,Garrett LE Jr,Thompson AL Jr,Collins NF,Lordon RE,Robinson RR, Fixed and reproducible orthostatic proteinuria: results of a 20-year follow-up study. Annals of internal medicine. 1982 Oct;     [PubMed PMID: 7125410]