Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
Advanced search 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 1516 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 

Table of Contents   
Year : 2020  |  Volume : 31  |  Issue : 2  |  Page : 515-520
Severe hyponatremia after donor nephrectomy

Department of Kidney Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Click here for correspondence address and email

Date of Submission20-May-2019
Date of Decision24-Jun-2019
Date of Acceptance25-Jun-2019
Date of Web Publication09-May-2020


Living kidney donation is safe and established but can lead to short- and long-term complications. Hyponatremia is the most common disorder of body fluid and electrolyte balance in clinical practice, associated with increased morbidity, mortality, and the length of hospital stay. A correct diagnosis of the etiology of hyponatremia is critical, both to determine correct management and prognosis. Here, we present a case of a severe hyponatremia following left- sided donor nephrectomy with a physical examination suggestive of mild hypovolemia. Laboratory tests revealed high urine osmolality and sodium concentration mimicking syndrome of inappropriate antidiuretic hormone secretion (SIADH), in the setting of abnormally blunted response to Synacthen. The patient responded well to hydrocortisone replacement. Differentiating between primary adrenal insufficiency and SIADH as a cause of severe hyponatremia was the key to successfully treating this patient. Hyponatremia following donor nephrectomy is unusual and could be explained in this case by hypocortisolism.

How to cite this article:
Ibrahim IA, Hassan EA, Ali TZ, Brockmann JG, Aleid HA. Severe hyponatremia after donor nephrectomy. Saudi J Kidney Dis Transpl 2020;31:515-20

How to cite this URL:
Ibrahim IA, Hassan EA, Ali TZ, Brockmann JG, Aleid HA. Severe hyponatremia after donor nephrectomy. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2021 Jun 23];31:515-20. Available from: https://www.sjkdt.org/text.asp?2020/31/2/515/284028

   Introduction Top

Living kidney donation decreases the expanding disparity between the need for and supply of renal allografts, and provide recipients the best chance for dialysis-free survival.[1] Living kidney donation is safe and established, but can result in long-term complications such as chronic fatigue.[2] Hyponatremia is the most fre- quently observed water-electrolyte imbalance met in clinical practice, and is associated with increased morbidity, mortality, and hospital length of stay.[3] In this case report, we describe a 60-year-old woman who presented with a severe hyponatremia after donor nephrectomy.

   Case Report Top

Informed consent was obtained from the patient before publishing the case.

A 60-year-old Saudi woman, with unremarkable previous medical history, underwent left- sided donor nephrectomy. One week after nephrectomy, she presented to the emergency department with five days history of diarrhea, abdominal pain, nausea and nonbloody, non- bilious vomiting. She did not smoke tobacco, drink alcohol, or use over-the-counter medications. There was no family history of malignant or autoimmune diseases.

On physical examination, her temperature was 36.7°C (98°F), pulse rate was 88 beats/ min, regular; and blood pressure (BP) was 115/70 mm Hg with mild postural drop. She seemed mildly dehydrated. Further physical examination did not reveal any abnormality. Intravenous access was obtained, and 500 mL of normal saline was administered before the laboratory test results were received.

Her laboratory tests on admission showed a severe hyponatremia (113 mmol/L), low plasma osmolality, and elevation of both urine osmolality and urine sodium concentration. In addition, normal anion-gap metabolic acidosis [renal tubular acidosis (RTA)] was also noted [Table 1]. The blood levels of other biochemical parameters were normal. A urine drug screen was negative. Further diagnostic studies including abdominal ultrasound, chest X-ray, and brain computed tomography, showed no abnormalities.
Table 1: Laboratory results.

Click here to view

Because of apparent hypovolemia (evidenced by the history of diarrhea, vomiting and postural BP drop), intravenous NaCl 0.9% was initiated, resulting in an initial rise of serum sodium levels (up to 128 mmol/L) over three days. This response was not sustained with subsequent drop in serum sodium levels down again to 113 mmol/L despite the absence of ongoing GI losses and continuation of NaCl 0.9% infusion. At this point, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was assumed. Fluid management was changed to NaCl 2% infusion with oral fluid restriction to 800 mL/day. Nevertheless, fluid therapy (NaCl 2% with fluid restriction) showed incomplete response in the form of initial rise (up to 130 mmol/L over 5 days) followed by plateauing of serum sodium levels.

Lacking an optimal response to treatment for SIADH and fluctuation in sodium levels, the diagnosis was reassessed, and adrenal insufficiency and/or hypothyroidism were suspected.

Further diagnostic tests were done. Serum thyroid-stimulating hormone was 6.3 mU/L (reference range, 0.27-4.2 mU/L) with free thyroxine of (T4) 7.6 pmol/L (reference range, 12-22 pmol/L) denoting primary hypothyroi-dism. Levothyroxine therapy was initiated but again with no much improvement.

The random serum cortisol concentration was 124 nmol/L (reference range: 150-700 nmol/L), and the short Synacthen stimulation test showed a baseline cortisol of 140 nmol/L (reference range: 171-536 nmol/L), which increased to 381 nmol/L (normal response: 500-550 nmol/L) denoting suboptimal response. Based on these results, the diagnosis of primary adrenal insufficiency was confirmed. Oral hydrocortisone was started (10-5 mg daily), which corrected serum sodium concentrations to levels within the reference range [Figure 1]. The patient’s clinical status improved promptly, and she was discharged home with standard replacement doses of hydrocortisone with normal repeat serum sodium levels on follow-up and later successful hydrocortisone discontinuation.
Figure 1: Serum sodium concentrations on admission, following subsequent treatment with fluid restriction, and hydrocortisone.

Click here to view

   Discussion Top

Our case demonstrates two main aspects. First, how difficult the diagnosis of hypo- natremia with high urine osmolality and urine sodium can be. Second, it exemplifies how elusive the phenotype of primary adrenal insufficiency can be.

Several diagnoses for our patient’s hypo- natremia that could explain the high urine sodium level and osmolality were considered.

The list comprises salt-wasting syndromes (cerebral and renal), diuretic use, and hormonal alterations (hypothyroidism, primary or secondary adrenal insufficiency, and SIADH).[4] SIADH is a diagnosis of exclusion that can be considered only if an alternative diagnosis is not identified.[4]

A number of diagnoses were ruled out like salt-wasting syndrome and diuretic use as there were no clues from history and brain imaging was unremarkable. The assessment of volume status is crucial to hyponatremia evaluation.[3] Our patient presented with initial mild extracellular volume depletion with restoration of euvolemia after fluid resuscitation. Other useful indices of the extracellular fluid volume during hyponatremia include serum uric acid levels which are usually low in cases of volume expansion (SIADH, hypocorti- solism) due to the inhibition of renal proximal tubular reabsorption and normal or increased in reduced extracellular fluid volume (diuretics, salt-wasting nephropathy, and primary adrenal insufficiency).[3] Exactly, how hypo- thyroidism induces hyponatremia is unclear but may be related to increased antidiuretic hormone release from the hypothalamus and disturbed sodium handling in the renal tubules.[3]

A propensity toward metabolic alkalosis implies diuretic use (hyperaldosteronism, possible contraction alkalosis) or SIADH, while metabolic acidosis proposes primary adrenal insufficiency.[4] Diuretic use would be anticipated to cause hypokalemia, while hyper- kalemia is more distinctive for primary adrenal insufficiency.[4]

Although SIADH is more common than adrenal insufficiency, the outcomes can be serious when adrenal insufficiency is over- looked.[5],[6] Patients with primary adrenal insufficiency without significant hypoaldosteronism may have euvolemic hyponatremia with a“SIADH-like” picture that is characterized by increased urinary osmolality and urine sodium concentration.[7] Primary adrenal insufficiency is suggested by low random cortisol concentrations, while normal concentrations still require an ACTH stimulation test for exclusion. The standard high-dose ACTH stimulation test (250 ęg synthetic ACTH 1-24 as an intravenous bolus) is a sensitive indicator of adrenocortical responsiveness, and it was validated for primary adrenal insufficiency.[8] A normal response to the high-dose ACTH (Synacthen) stimulation test is a rise in serum cortisol concentration after either 30 or 60 min to a peak of 500 nmol/L or higher.[8]

Adrenal insufficiency must always be excluded in the cases of severe hyponatremia, as the classic clinical and biochemical features may not be present. Primary adrenal insufficiency can present without some typical features such as pigmentation, orthostatic hypotension, hyperkalemia, hypoglycemia, and hypercal- cemia. The patient we illustrate presented with normal anion-gap metabolic acidosis without hypotension and hyperkalemia. Two possible mechanisms might explain this scenario: First, isolated hypocortisolism with enough aldos- terone remaining to prevent renal sodium loss and permit potassium secretion. A second possible theory is the presence of defense mechanisms that prevented hypotension and hyperkalemia despite aldosterone deficiency.[9] Mild normal anion-gap metabolic acidosis (despite the vomiting) in our case stems from a hypoaldosteronism-associated RTA causing defective urinary acidification.[9]

Cortisol deficiency causes hyponatremia because it increases CRH production, which promotes antidiuretic hormone release,[10] whereas aldosterone deficiency causes hypo- natremia because of renal tubular sodium loss, hypovolemia, and baroreceptor-mediated anti- diuretic hormone release.[11],[12]

Cherney et al hypothesized three explanations why a substantial sodium deficit does not necessarily cause hemodynamic instability.[13] First, hyponatremia will produce red blood cell swelling, which will increase plasma volume and hence the effective circulating volume. Second, imminent hypovolemia will generate a high adrenergic state, causing venous vaso- constriction, lessening the size of the vascular compartment and permitting better filling pressures. Third, hyponatremia implies cell swelling, which will increase interstitial pressure and may shift volume from the interstitial space to the intravascular space.[13]

In addition to hypotension, hyperkalemia occurs in only 50%-60% of patients with primary adrenal insufficiency.[6],[14] Possible confounding factors are a low dietary intake of potassium (loss of appetite is common in adrenal insufficiency) and gastrointestinal losses of potassium through diarrhea and vomiting.

In this case, severe hyponatremia was the most prominent feature of primary adrenal insufficiency. Adrenal insufficiency should always be excluded in individuals with unexplained hyponatremia who have high urine sodium and osmolality before diagnosing SIADH.

Several studies have assessed the health- related quality of life (HRQoL) following kidney donation. A systematic review of these data revealed that shortly after donation, donors experience a poorer HRQoL, and minor-to-moderate changes in psychological and social-relational functioning which returns to baseline 3-12 months postdonation.[15] Some studies has postulated possible endocrino- logical explanations for some of the post donation complications, especially chronic fatigue.[16],[17]

A recent prospective open-label monocentric cohort study was designed to test adrenal function after laparoscopic hand-assisted donor nephrectomy.[16] The study yielded a key finding of transiently and significantly reduced adrenocortical responsiveness (measured with low-dose ACTH stimulation test) after left- sided living donor nephrectomy compared with the right-sided one. Their data showed that this disrupted cortisol response resolved after 28 days. As the adrenal vein is usually transected during left-sided donor nephrec- tomy, which is not mandatory on the right side, they postulated that venous congestion could result in an impairment of adrenal function. The left adrenal gland is more manipulated during surgery, adding further injury.[16] This theory of adrenal injury due to interruption of the venous drainage of the left adrenal gland during left-sided donor nephrec- tomy might explain the adrenal insufficiency in our case.

   Conclusion Top

In this case with complex hyponatremia following donor nephrectomy, a mechanism of severe hyponatremia caused by primary adrenal insufficiency, could be due to disruption of the venous drainage of the left adrenal gland during left-sided donor nephrectomy with subsequent venous congestion and adrenal malfunction; for which the administration of hydrocortisone demonstrated further therapeutic efficacy. Further observational prospective studies of adrenal function following donor nephrectomy are needed to verify this proposed mechanism.

Conflict of interests: None declared.

   References Top

Lentine KL, Patel A. Risks and outcomes of living donation. Adv Chronic Kidney Dis 2012;19:220-8  Back to cited text no. 1
Lam NN, Lentine KL, Levey AS, Kasiske BL, Garg AX. Long-term medical risks to the living kidney donor. Nat Rev Nephrol 2015; 11:411-9  Back to cited text no. 2
Hoorn EJ, Zietse R. Hyponatremia revisited: Translating physiology to practice. Nephron Physiol 2008;108:p46-59  Back to cited text no. 3
Decaux G, Musch W. Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol 2008;3:1175-84  Back to cited text no. 4
Smith JC, Siddique H, Corrall RJ. Misinterpretation of serum cortisol in a patient with hyponatraemia. BMJ 2004;328:215-6  Back to cited text no. 5
Soule S. Addison’s disease in Africa—a teaching hospital experience. Clin Endocrinol (Oxf) 1999;50:115-20  Back to cited text no. 6
Kinjo T, Higuchi D, Oshiro Y, et al. Addison’s disease due to tuberculosis that required differentiation from SIADH. J Infect Chemother 2009;15:239-42  Back to cited text no. 7
Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med 2003; 139:194-204  Back to cited text no. 8
van der Hoek J, Hoorn EJ, de Jong GM, Janssens EN, de Herder WW. Severe hypo- natremia with high urine sodium and osmo- lality. Clin Chem 2009;55:1905-8  Back to cited text no. 9
Schrier RW. Body water homeostasis: Clinical disorders of urinary dilution and concentration. J Am Soc Nephrol 2006;17:1820-32  Back to cited text no. 10
Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003;361:1881-93  Back to cited text no. 11
Ohara M, Cadnapaphornchai MA, Summer SN, et al. Effect of mineralocorticoid deficiency on ion and urea transporters and aquaporin water channels in the rat. Biochem Biophys Res Commun 2002;299:285-90  Back to cited text no. 12
Cherney DZ, Davids MR, Halperin ML. Acute hyponatraemia and ’ecstasy’: Insights from a quantitative and integrative analysis. QJM 2002;95:475-83  Back to cited text no. 13
Gagnon RF, Halperin ML. Possible mechanisms to explain the absence of hyperkalaemia in Addison’s disease. Nephrol Dial Transplant 2001;16:1280-4  Back to cited text no. 14
Wirken L, van Middendorp H, Hooghof CW, et al. The course and predictors of health- related quality of life in living kidney donors: A systematic review and meta-analysis. Am J Transplant 2015;15:3041-54  Back to cited text no. 15
Burn F, Schirpenbach C, Bidlingmaier M, et al. Left-sided living kidney donation leads to transiently reduced adrenocortical responsiveness. Am J Transplant 2017;17:1879-84  Back to cited text no. 16
Schachtner T, Reinke P. Left-sided donor nephrectomy predisposes living kidney donors to latent adrenal insufficiency with symptoms of fatigue and inferior quality of life. Am J Transplant 2017;17 Suppl 3. https://atcmeetingabstracts.com/abstract/left- sided-donor-nephrectomy-predisposes-living- kidney-donors-to-latent-adrenal-insufficiency- with-symptoms-of-fatigue-and-inferior- quality-of-life/. [Last accessed on 2018 Nov 13].  Back to cited text no. 17

Correspondence Address:
Ihab A Ibrahim
Department of Kidney and Pancreas Transplantation, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211
Saudi Arabia
Login to access the Email id

DOI: 10.4103/1319-2442.284028

PMID: 32394926

Rights and Permissions


  [Figure 1]

  [Table 1]


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded139    
    Comments [Add]    

Recommend this journal