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Issues Affecting the Kidneys and Bladder

Mitochondrial disease affecting the kidney usually involves the proximal tubules. Ninety percent of oxygen consumption by the kidney is used to generate ATP for Na+/K+ ATPase in the proximal tubules and ascending loop of Henle (Chinnery, 1997). Dysfunction results in renal Fanconi syndrome (Kuwertz-Broking, 2000; Wang, 2000) with urinary losses of electrolytes, glucose, bicarbonate, amino acids, calcium and phosphate, and water. This occurs more often in children than adults. Loss of phosphate can result in rickets and loss of water can produce a dehydrated state. The loss of bicarbonate and subsequent metabolic acidosis can be associated with failure to thrive.

Less common presentations include more isolated renal tubular acidosis, Bartter syndrome (Emma, 2006), nephrotic syndrome associated with glomerulosclerosis (Goldenberg, 2005) and tubulo-interstitial nephropathy.

When bladder dysfunction occurs, patients may complain of frequency, urgency, incomplete emptying ("double-voiding"), and/or frank urinary retention. When severe, these can result in vesico-ureteral reflux and/or urinary tract infections and potentially urosepsis. The onset of these symptoms may be gradual, or initially may not be an issue except during periods of physiologic stress (e.g., during infections) with a return to regular functioning as the stressor recedes. With disease progression, the symptoms may become more persistent. The urinary symptoms can occur in association with severe constipation (and ileus) (Garcia-Velasco, 2003).

Mitochondrial disease patients may have significant autonomic dysregulation (Zelnik, 1996; Axelrod, 2006). Those with significant autonomic dysfunction (especially vascular dysautonomia) appear to have a higher fluid requirement than usual. Failure to meet that increased need may lead to state characterized by fatigue, dizziness, and production of an unexpectedly concentrated urine (as if the patient is hypovolemic). The latter may occur even though documentation may show a reasonable fluid intake. Responding with enough fluid to create a more dilute urine (specific gravity =<1.015 or urine osmolality =<450) can help to relieve the symptoms and increase urine output.

As the disease progresses and the vascular dysautonomia worsens, orthostasis becomes a more serious issue. Unless more fluid is provided, the patient may develop tachycardia and hypotension. Fluid requirements can be impressive and may far exceed typical maintenance volumes. This results in chronic polyuria. An attempt to cut back on fluids prompts a recurrence of the orthostatic findings.


1. Assess hydration and actual fluid intake.

2. Measure vital signs including blood pressure.

3. Assess bladder function - frequency, urgency, volume, incontinence.

4. Urinalysis and microscopic analysis of urine sediment.

5. Assess urine concentration (urine specific gravity or osmolality). If urine production is low or the urine unexpectedly concentrated given the fluid intake, consider the presence of vascular dysautonomia and a suboptimal fluid intake.

6. Is there a history of infections in the bladder and kidney.

7. Is there a history or evidence of growth failure (suggesting ongoing metabolic acidosis) or rickets?


  1. If there is a history of autonomic dysfunction +/- a history of adequate fluid intake, the patient might have a higher fluid requirement. Assess urine concentration and provide extra fluids (either enterally or intravenously). If the patient's gut cannot accommodate an appropriate increase in fluid (because of limited motility), IV fluids should be considered. Infusions of fluid over several hours might provide a long-lasting effect than boluses over 1-2 hours.
  2. When the patient has symptoms suggestive of retention with frequency and "double-voiding," having the patient try and urinate on a schedule (e.g., every two hours) may help reduce the incidence of infection (as well as other symptoms such as urgency, frequency, dribbling and incontinence). Prophylactic antibiotics may be a consideration. In more advanced cases, intermittent catheterization may be indicated. A urologic evaluation can help provide guidance and direction.
  3. If there is a history of or evidence for growth failure or rickets, assess for renal tubular dysfunction including blood electrolytes, bicarbonate and phosphorus, urinalysis (including glucose and pH), and urine for amino acids.
  4. If evidence of tubular dysfunction or other renal disease, consider referral to a nephrologist.


Axelrod FB, Chelimsky G, Weese-Mayer DE. Pediatric autonomic disorders. Pediatrics 2006;118:309-21.

Chinnery PF, Turnbull DM. Mitochondrial Medicine. Oxford University Press. Vol 90(11). pp. 657-667. November, 1997.

Emma F, Pizzini C, Tessa A, et al. "Bartter-like" phenotype in Kearns-Sayre syndrome. Pediatr Nephrol 2006;21:355-60.

Garcia-Velasco A, Gomez-Escalonilla C, Guerra-Vales JM, et al. Intestinal pseudo-obstruction and urinary retention: Cardinal features of a mitochondrial DNA-related disease. J Intern Med 2003;253:381-5.

Goldenberg A, Ngoc LH, Thouret MC, et al. Respiratory chain deficiency presenting as congenital nephrotic syndrome. Pediatr Nephrol 2005;20:465-9.

Kuwertz-Broking E, Koch HG, Marquardt T, et al. Renal Fanconi syndrome: First sign of partial respiratory chain complex IV deficiency. Pediatr Nephrol 2000:14:495-8.

Rotig A, Niaudet P. Mitochondrial nephrology. In Mitochondrial Medicine. DiMauro S, Hirano M, Schon EA, eds. Informa Healthcare, Abingdon UK, 2006, 1197-208.

Wang LC, Lee WT, Tsai WY, et al. Mitochondrial cytopathy combined with Fanconi's syndrome. Pediatr Neurol 2000;22:403-6.

Zelnik N, Axelrod FB, Leschinsky E, et al. Mitochondrial encephalomyopathies presenting with features of autonomic and visceral dysfunction. Pediatr Neurol 1996;14:251-4.

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