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  Table of Contents  
EDITORIAL COMMENTARY
Year : 2011  |  Volume : 21  |  Issue : 3  |  Page : 152-153
 

Urinary indices in nephrotic syndrome


Department of Nephrology, Osmania General Hospital, Osmania Medical College, Hyderabad, Andhra Pradesh, India

Date of Web Publication17-Aug-2011

Correspondence Address:
M Sahay
6-3-852/A, Ameerpet, Hyderabad - 500 016, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-4065.83027

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How to cite this article:
Sahay M. Urinary indices in nephrotic syndrome. Indian J Nephrol 2011;21:152-3

How to cite this URL:
Sahay M. Urinary indices in nephrotic syndrome. Indian J Nephrol [serial online] 2011 [cited 2018 Dec 16];21:152-3. Available from: http://www.indianjnephrol.org/text.asp?2011/21/3/152/83027


Nephrotic patients with edema may have variable volume status i.e. hypo, hyper or normovolemia. Volume-expanded patients may benefit with diuretics while volume-contracted patients need volume expansion. [1] Clinically it is not possible to differentiate severely edematous nephrotic syndrome (NS) patients with intravascular volume expansion (VE) from those with intravascular contraction (VC). [2] Hence urine indices may have some role in elucidating the volume status. Since severe hypoalbuminemia is commoner in children, these indices may be more important in the management of NS in the pediatric population.


  Pathogenesis of Edema Top


It is important to be aware of the pathogenesis of edema in NS in order to understand the principle behind measurement of urinary indices. The historical theory of nephrotic edema generation postulates that stimulation of the renin-aldosterone axis (RAAS) in response to hypovolaemia mediates sodium retention through the following sequence of events: Low serum albumin with decreased plasma oncotic pressure results in an imbalance of Starling forces in capillaries leading to interstitial leakage of fluid, low oncotic pressure, hypovolaemia and stimulation of the RAAS system. [3] This is termed as the underfill hypothesis.

However, many workers do not support the underfill theory, and focus on the conceptually opposite idea, the so-called "overfill" hypothesis of primary sodium retention in at least some patients. [4] The classic studies by Chandra et al.,[5] demonstrated that proteinuria per se results directly in sodium retention. They showed that hypoalbuminemia and hypovolemia are not essential for sodium retention.

The site of increased sodium absorption in the kidney remains controversial. In the study by Ichikawa et al.,[6] the collecting duct was found to be the main site for sodium reabsorption with increased sodium transport via epithelial sodium channel ENaC and sodium potassium adenosine triphosphatase [Na-K-ATPase]. [7] Valentin et al. showed that cyclic guanosine monophosphate cGMP phosphodiesterase activity in the medullary collecting ducts is increased, leading to resistance to atrial natriuretic peptide actions thus causing sodium retention. [8] In contrast, some studies have supported the proximal tubule as the site of increased sodium reabsorption in NS with albumin directly stimulating NHE3 (sodium hydrogen exchanger 3). [9] Thus the relative importance of the role of the proximal tubule and collecting duct in sodium absorption is controversial.


  Urine Indices in Nephrotic Syndrome Top


Even though the site of sodium reabsorption remains controversial, it is abundantly clear that edema in nephrotic patients may be associated with either low or increased intravascular volume and identification of volume status is important for therapy. In patients with intravascular volume depletion IV albumin may be needed while in edema associated with renal sodium retention diuretics are indicated.

Urine indices may be useful for determining the volume status associated with nephrotic edema. The common urine indices used for determining volume status are the following:

  1. Fractional excretion of sodium (Fe Na )= (S Cr × U Na ) / (S Na × U Cr ) ×100 where SCr is serum creatinine (mg/dl), UNa is urinary sodium (meq/l), SNa is serum sodium (meq/l)and UCr is urine creatinine (mg/dl). FeNa is low < 0.2 ± 0.2 % in the VC group in contrast to the VE group. [10]
  2. Urine Potassium index (UK+ /UK+ +UNa+ ). UK+ is urine potassium in spot urine sample (meq/l) while UNa+ is urine sodium (meq/l). In VC states due to associated secondary hyperaldosteronism urine potassium excretion is high. In contrast, patients with VE have low urine K excretion. Thus in VC states urine K index is >0.6 (or 60% if expressed as %) while in VE states urine K index is < 0.6. [11] A fresh second voided morning spot urine sample is recommended for albumin, sodium, potassium and creatinine estimation. A simultaneous serum sample should be collected to measure sodium, potassium, albumin and creatinine values. Patients should be on normal salt and water intake. Diuretics, angiotensin enzyme inhibitors and angiotensin receptor blockers may interfere with urine indices and hence should not be used before the urine indices have been tested or diuretics should be discontinued for at least 8 h.



  Other Indicators of Volume Status Top


VC patients may have postural hypotension; their serum albumin is generally <2 g/dl. In addition, VC patients have significantly higher blood urea nitrogen (BUN) and BUN/creatinine ratio compared with VE patients. Mean hemoglobin/hematocrit, urine osmolality, and urine-to-serum osmolality ratio (UOsm /SOsm ), may be higher in the VC group compared with the VE group. VC patients have higher renin, aldosterone, and anti-diuretic hormone (ADH) concentration in comparison to the VE group. These tests are, however, expensive and not available at all centers. Hence, urine indices can be useful surrogate markers for volume status.


  Limitations of Urine Indices Top


Use of diuretics or angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may interfere with the use of urinary indices. Salt intake may influence the urinary indices hence the patients should be on normal salt diet during evaluation. The urine indices do not differentiate between minimal change disease and the non-minimal change variety of NS. Also, the urine indices cannot differentiate between the steroid responders and non-responders as has been highlighted in this issue of the journal.


  Conclusion Top


Measurement of urine indices is a simple bedside tool, and can be used for volume assessment in nephrotic patients. Low sodium excretion coupled with high urinary potassium indicates hypovolemia. Such patients should not receive oral or intravenous diuretics, before correction of their intravascular volume with either crystalloids or colloids. Patients with edema and no clinical or laboratory features of hypovolemia (normal levels of blood urea, FeNa not <0.2% and urinary K+ / K+ + Na+ <60%) can safely be treated with potent diuretics.

 
  References Top

1.Iyengar AA, Kamath N, Vasudevan A, Phadke KD. Urinary indices during relapse of childhood nephrotic syndrome: Does it help the clinician in management of edema?. Indian J Nephol 2011[In Press].   Back to cited text no. 1
    
2.Schrier RW, Fassett RG. A critique of the overfill hypothesis of sodium and water retention in the nephrotic syndrome. Kidney Int 1998;53:1111-7.  Back to cited text no. 2
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3.Epstein A. Concerning the causation of edema in chronicparenchymatous nephritis: Methods for its alteration. Am J Med Sci 1917;154:638-47.  Back to cited text no. 3
    
4.Joles JA, Willekes-Koolschijn N, Braam B, Kortlandt W, Koomans HA, Dorhout Mees EJ. Colloid osmotic pressure in young analbuminemic rats. Am J Physiol 1989;257:F23-8.   Back to cited text no. 4
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5.Chandra M, Hoyer JR, Lewy JE. Renal function in rats with unilateral proteinuria produced by renal perfusion with aminonucleoside. Pediatr Res 1981;15:340-4.  Back to cited text no. 5
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6.Ichikawa I, Rennke HG, Hoyer JR, Badr KF, Schor N, Troy JL, et al. Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome. J Clin Invest 1983;71:91-103.  Back to cited text no. 6
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7.Deschenes G, Wittner M, Stefano A, Jounier S, Doucet A. Collecting duct is a site of sodium retention in PAN nephrosis: Arationale for amiloride therapy. J Am Soc Nephrol 2001;12:598-601.  Back to cited text no. 7
    
8.Valentin JP, Ying WZ, Sechi LA, Ling KT, Qiu C, Couser WG, et al. Phosphodiesterase inhibitors correct resistance to natriureticpeptides in rats with Heymann Nephritis. J Am Soc Nephrol 1996;7:582-93.  Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Klisic J, Zhang J, Nief V, Reyes L, Moe OW, Ambühl PM. Albumin regulates the Na_/H_ exchanger 3 in OKP cells. J Am Soc Nephrol 2003;14:3008-16.  Back to cited text no. 9
    
10.Kapur G, Valentini RP, Imam AA, Mattoo TK. Treatment of severe edema in children with nephrotic syndrome with diuretics alone: A prospective study. Clin J Am Soc Nephrol 2009;4:907-13.  Back to cited text no. 10
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11.Donckerwolcke RA, France A, Raes A, Vande Walle J. Distal nephron sodium-potassium exchange in children with nephrotic syndrome. Clin Nephrol 2003;59:259-66.  Back to cited text no. 11
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