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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2013  |  Volume : 24  |  Issue : 6  |  Page : 1217-1222
Refeeding syndrome in a patient with advanced Kidney failure due to Nephronophthisis


Department of Medicine, Faculty of Medicine, Kuwait University, Safat, Kuwait

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Date of Web Publication13-Nov-2013
 

   Abstract 

Refeeding syndrome (RS) is a serious and potentially fatal disorder. It is caused by a shift of fluids, sodium, potassium, magnesium and phosphorus as well changes in the metabolism of glucose, protein, fat and vitamins following the refeeding of malnourished patients, whether enterally or parenterally. RS has rarely been reported in patients with advanced kidney disease probably due to the pre-existing hyperphosphatemia, hypermagnesemia and hyperkalemia in these patients. In the following report, we present a patient with nephronophthisis type 1 deletion syndrome in whom her main previous nutrition was limited to simply rehydration to avoid renal replacement therapy. On presentation, she was cachectic and dehydrated with advanced kidney failure. She was treated with medical nephrectomy using non-steroidal anti-inflammatory drugs and then placed on maintenance hemodialysis. Percutaneous endoscopic gastrostomy was used for her initial feeding. Care was exercised during her early refeeding with regard to correction of fluids and essential electrolytes, viz. potassium, phosphorus and magnesium, as well as multivitamins to avoid the cardiovascular and neurological complications of RS. However, the changes in the gut, pancreas and liver as well as her hyperlipidemia were a clear obstacle. Fortunately, the ileus and pancreatitis she developed on refeeding improved dramatically with a decrease of the feeding dose to half; however, the liver abnormalities and hyperlipidemia were severe and slow to recover. These improved after addition of ursodeoxycholic acid and permitted successful increase of the dose of feeding subsequently.

How to cite this article:
El-Reshaid K. Refeeding syndrome in a patient with advanced Kidney failure due to Nephronophthisis. Saudi J Kidney Dis Transpl 2013;24:1217-22

How to cite this URL:
El-Reshaid K. Refeeding syndrome in a patient with advanced Kidney failure due to Nephronophthisis. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Aug 23];24:1217-22. Available from: http://www.sjkdt.org/text.asp?2013/24/6/1217/121304

   Introduction Top


Refeeding syndrome (RS) is a serious and potentially fatal disorder in patients supported enterally or parenterally. It is caused by an intracellular shift of fluids, sodium, potassium, magnesium and phosphorus as well as well changes in the metabolism of glucose, protein, fat and vitamins resulting from the enhanced insulin secretion in response to caloric load. [1] During prolonged starvation, the above-mentioned minerals become severely depleted; however, their serum concentrations may remain normal as these ions that are mainly intracellular come out from the cells when the intracellular compartment contracts during starvation. In addition, starvation is also associated with a reduction in their renal excretion. [2] Severe hypophosphatemia is the hallmark of the syndrome and is responsible for cardiovascular collapse, rhabdomyolysis and seizures due to depletion of adenosine triphosphate (ATP), which is the energy store, leading to tissue hypoxia and impaired muscle contraction, including the myocardium. [3] Moreover, increased fluid intake associated with poor myocardial mass and contractility can lead to massive edema and heart failure. Hypokalemia, hypomagnesemia and hypophosphatemia are major factors in the associated cardiac arrhythmias and sudden death associated with this syndrome. [4] Wernicke's encephalopathy, manifesting as delirium, can occur rapidly in these patients while they are usually thiamine deficient following high-calorie feeding. [5] RS has been rarely reported in patients with advanced kidney disease probably due to the pre-existing hyperphophatemia, hypermagnesemia and hyperkalemia in these patients. In the following report, we present our experience in the management of such a patient and highlight the various aspects of its presentation, which were far beyond an acute derangement of minerals in the serum.


   Case Report Top


On August 2009, a 26-year-old mentally subnormal Pakistani woman was brought by her parents for failure to thrive and advanced kidney failure with a serum creatinine of 500 μmol/L. She had been evaluated at various centers in Pakistan and Kuwait. Because she was dehydrated on each of her previous presentations, she was treated with plain intravenous fluids to correct the dehydration and was sent home. The family acknowledged that her consciousness improved after this maneuver; however, she remained with poor appetite and failure to thrive in between. The frequency of such hospital admissions increased in the past year and she hardly was at home for more than 1 week without the need for intravenous rehydration. The parents denied fever, shortness of breath, cough, joint pains, edema or skin rash. The patient is an older sister of a boy who is similarly mentally subnormal. She did not have a previous medical disease, allergy and surgery or had used any regular medications.

On her initial physical examination, the patient was conscious and oriented. She did not have any pain or shortness of breath. She was cachectic, with a weight of 39 kg, but with a height of 1.5 m. Her blood pressure was 80/40 mmHg while lying, and was unrecordable on standing. Her temperature was normal. She did not have lymphadenopathy, goiter, jugular venous distension or edema. Systemic examination showed psychomotor delay, hypotonia, occulomotor apraxia, sensorineural deafness and retinitis pigmentosa. Apart from these, systemic examination did not show any significant abnormality.

Laboratory investigations showed normal peripheral leucocytic and platelets counts. Hemoglobin was 90 g/L with normal mean corpuscular volume(MCV). ESR was 10 mm/h. Serum sugar was normal. Serum urea and creatinine were elevated at 37 mmol/ L and 500 μmol/L, respectively. Serum electrolytes showed normal electrolytes except for mildly elevated phosphorus [Table 1]. Serum bilirubin, ALT and AST were normal. Alkaline phosphatase was raised but the gamma GT was normal. Parathyroid hormone was 127. Serum albumin was low at 31 g/L. Serum CPK, amylase, cholesterol and TSH were all normal. Urine routine and microscopy were also normal. Blood culture was negative. Widal test,  Brucella More Details slide agglutination test, viral tests for CMV, EBV, herpes virus and hepatitis B and C were negative. Serum complements (C3 and C4) and protein electrophoresis were normal except for hypoalbuminemia. ANA, anti-ds DNA, ANCA, RA factor, cryoglobulins and anti-mitochondrial antibodies were negative. Stool testing for ova, parasites and occult blood was normal. Chest X-ray and ECG were normal. Abdominal and pelvic ultrasound did not show abnormality except for bilateral small and echogenic kidneys with few cortical cysts in both. The patient was treated initially with normal saline, with correction of potassium, phosphorus and magnesium, which were anticipated to decrease with volume expansion and improvement of her pre-renal acute renal failure state. As expected, she improved and regained consciousness and orientation. Her serum urea and creatinine decreased to 18 mmol and 427 μmol/L, respectively [Table 1]. At this stage, she was noted to be still extremely weak and unable to eat or drink enough fluids. After obtaining consent from her parents, a percutaneous endoscopic gastrostomy (PEG) tube was fixed on 7 September 2009. She received fluids alternating with nearly four to five cans of Ensure daily. Two days later, she developed severe abdominal pain with distension and poor bowel sounds, and plain X-ray abdomen showed multiple fluid levels. Laboratory investigations showed mildly elevated bilirubin, ALT, AST, alkaline phosphatase and gamma GT, amylase and lipase. A CT scan of the abdomen did not show any abnormality in the liver, bile ducts or pancreas. Laparoscopic exploration did not show any evidence of perforation and the PEG tube was found to be well placed in position. She was treated with nasogastric suction and IV fluids that contained dextrose with ½ normal saline only with appropriate electrolytes and multivitamins. She improved gradually over few days. Subsequently, PEG feeding was resumed. The parents were informed that the patient already has an advanced chronic kidney disease and that she needed maintenance dialysis. The doctors also mentioned the fact that she had a salt losing state that was responsible for her recurrent dehydration. They agreed for medical nephrectomy with non-steroidal anti-inflammatory drugs (NSAIDs) and placed her on maintenance hemodialysis. The use of NSAIDs in this patient was not without a risk despite omeperazole 20 mg twice daily. In the third week, she developed severe upper gastrointestinal bleed that was due to two large ulcers, which stopped bleeding after alcohol injections. NSAIDs were discontinued and the bleeding never recurred. Subsequently, the patient gradually improved but had an enlarged liver with raised liver enzymes in a cholestatic pattern as well as high amylase, lipase and lipids [Table 1]. Repeat ultrasound of the abdomen did not show any abnormality except the enlarged liver with increased echogenicity. At this stage, liver biopsy was considered. However, the risk of bleeding with the percutaneous approach is high and the transjugular route is difficult with an already inserted permacath in the superior vena cava. At this stage, two decisions were made. The first was to decrease her Ensure feed to only two cans daily. This stabilized her general condition but, unfortunately, did not improve her liver functions. The second was to add ursodeoxycholic acid (ursofalk), which improved her liver functions. The later was given one capsule thrice daily for 2 weeks, which was doubled to two, thrice daily after that. After a few weeks of gradual improvement of her liver and pancreatic enzymes, the dose of Ensure was increased and was back to 4 - 5 cans/day. At the same time, the parents were able to feed her orally and she tolerated both types of feeding. Her last amylase and lipase are normal. Her liver enzymes are almost normal with normal liver, bile ducts, portal vein and spleen on ultrasonography. She gained 15 kg since her initial admission and she is back to her school. The PEG tube will be removed soon as she is already achieving adequate oral feeds without dehydration and her family is keen for kidney transplantation.
Table 1: Flow chart showing serial changes in biochemical parameters in the patient.

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   Discussion Top


Our patient presented with chronic renal failure, dehydration and cachexia. Her age of presentation, small-sized kidneys, salt losing state, associated neurological abnormalities, retinitis pigmentosa and family history are compatible with nephronophthisis type 1 deletion syndrome. [6] However, her cachexia was clearly due to an inadvertent neglect of the treating physicians caring for such a patient with advanced kidney disease and limiting her nutrition to simply rehydration and avoiding renal replacement therapy that was inevitable. The most urgent measure to stabilize her intravascular volume was to prevent the loss of fluids and electrolytes from her kidneys. Medical nephrectomy using NSAIDs [7] was the most practical approach and, subsequently, she tolerated maintenance hemodialysis. Care was exercised during her early refeeding with regard to correction of fluids and essential electrolytes, viz. potassium, phosphorus and magnesium, as well as multivitamins to avoid the cardiovascular and neurological complications of RS. However, hyperlipidemia and the changes in the gut, pancreas and liver were a clear obstacle. Fortunately, the ileus and the pancreatitis improved dramatically with a decrease of the feeding dose to half; however, hyperlipidemia and the liver abnormalities were severe and slow to recover. Fortunately, they improved after addition of ursofalk and permitted successful increase of the dose of the feeding subsequently.

In early starvation with deficient carbohydrate intake and declining glycogen stores, the body adjusts by a series of metabolic and hormonal changes, switching from the use of carbohydrate to using fat and protein as the main source of energy and hence the basal metabolic rate decreases by as much as 20-25%. [2] The latter is achieved via gluconeogenesis and formation of ketone bodies useful for brain energy. However, during prolonged fasting, hormonal and metabolic changes are aimed at preventing protein and muscle breakdown. Muscle and other tissues decrease their use of ketone bodies and use fatty acids as the main energy source and the liver decreases its rate of gluconeogenesis thus preserving muscle protein. [2] Upon refeeding, i.e. carbohydrate load, acute and life-threatening events may develop due to the insulin surge and may produce the hypophosphatemia, hypokalemia and hypomagnesemia as described before. Moreover, care should be exercised with the choice of parenteral replacement fluids as excessive chloride salts may cause metabolic acidosis while acetate-based fluids produce alkalosis. [8] Bed-ridden patients may present with hypercalcemia at the start due to immobilization; however, on refeeding and mobilization, this improves. However, severe osteomalacia may exist in these patients and, if untreated, may manifest with serious fractures. [8] Our patient had severe osteodystrophy with high alkaline phosphatase on presentation but normal gamma GT, indicating bone disorder. Once the hypercalcemia improved with immobilization, she was treated with calcium and one alfa. Within the first 2 days after PEG feeding, the patients developed severe ileus and pancreatitis. A CT scan of the abdomen ruled out any collection or lesion in the pancreatic bed. The negative laparoscopy was reassuring that she had just another manifestation of RS. [9] In fact, the two disorders improved after temporary discontinuation of the PEG feed and, later, restarting with half of the recommended dose showed that she tolerated the feeds well. Lastly, her hyperlipidemia and abnormal liver function were a major concern and slow to recover even with reduction of the feeding dose. Hyperlipidemia did not improve with addition of a statin drug, indicating that the etiology is unlikely to be an over production. However, both improved after starting of ursofalk, indicating steatohepatitis. [10] In the general population, the overall frequency of liver complications associated with parenteral nutrition (PN) ranges from 7.4 to 84%, [11] with nearly 15-40% patients developing end-stage liver disease. [12] This wide variation in the reported frequency is the result of heterogeneity in the population studied, duration and composition of the PN. [13] With refeeding, steatosis, staetohepatitis, cholestasis and cholelithiasis have been described. [8] Ultrasound examination excluded cholelithiasis or extrahepatic biliary tract disease and showed only an enlarged and echogenic liver without splenomegaly. With regard to her liver disease, distinctive histopathological findings have been described in patients with PN-associated liver dysfunction. These include periportal inflammation, bile duct proliferation, portal bridging, canalicular and interlobular cholestasis, pigmented Kupffer cells, pseudoacinar formation, portal - portal bridging, fatty droplets, pericellular and portal fibrosis and cirrhosis. [14],[15] The persistent liver abnormalities that included elevated transaminases and only partially reversed even after resolution of hyperlipidemia is in favor of steatohepatitis rather than simple steatosis (fatty liver). The exact etiology is poorly understood in this condition; however, our patient improved after ursofalk therapy, which should be considered in the management of such patients.

 
   References Top

1.Hearing SD. Refeeding syndrome. BMJ 2004; 328:908-9.  Back to cited text no. 1
    
2.McCray S, Walker S, Parrish CR. Much ado about refeeding. Pract Gastroenterol 2004;28: 26-44.  Back to cited text no. 2
    
3.Perrault MM, Ostrop NJ, Tierney MG. Efficacy of intravenous phosphate replacement in critically ill patients. Ann Phamacother 1997; 31:683-8.  Back to cited text no. 3
    
4.Miller SJ. Death resulting from overzealous total parenteral nutrition: The refeeding syndrome revisited. Nutr Clin Pract 2008;23:166-71.  Back to cited text no. 4
    
5.Reuler JB, Girad DE, Cooney TG. Current concepts. Wernike's encephalopathy. N Engl J Med 1985;312:1035-9.  Back to cited text no. 5
    
6.Caridi G, Dagnino M, Rossi A, et al. Nephronophthisis type 1 deletion syndrome with neurological symptoms: Prevalence and significane of the association. Kidney Int 2006;70:1342-7.  Back to cited text no. 6
    
7.Olivera JJ, Frommer JP, Gonzalez JM. Medical nephrectomy: The last resort for intractable complications of the nephrotic syndrome. Am J Kidney Dis 1993;21:260-3.  Back to cited text no. 7
    
8.Btaiche IF, Khaldi N. Meatbolic complications of parenteral nutrition in adults, part 2. Am J Healt Syst Pharm 2004;61:2050-7.  Back to cited text no. 8
    
9.Keane FB, Fennell JS, Tomkin GH. Acute pancreatitis, acute gastric distension and duodenal ileus following refeeding in anorexia nervosa. Ir J Med Sci 1978;147:191-2.  Back to cited text no. 9
    
10.Spagnuolo MI, Iorio R, Vegnente A, Guarino A. Ursodeoxycholic acid for treatment of cholestasis in children on long-term total parenteral nutrition: A pilot study. Gastroenterology 1996;111:716-9.  Back to cited text no. 10
    
11.Kelly DA. Liver complications of pediatric parenteral nutrition-epidemiology. Nutrition 1998;14:153-7.  Back to cited text no. 11
    
12.Chan S, McCowen KC, Bistrian BR, et al. Incidence, prognosis, and etiology of end-stage liver disease in patients receiving home parenteral nutrition. Surgery 1999;126:28-34.  Back to cited text no. 12
    
13.Btaichi IF, Khaldi N. Parenteral nutrition-associated liver complications in children. Pharmacotherapy 2002;22:188-211.  Back to cited text no. 13
    
14.Baker Al, Rosenberg IH. Hepatic complications of total parenteral nutrition. Am J Med 1987;82:489-97.  Back to cited text no. 14
    
15.Payne-James JJ, Silk DB. Hepatobilialy dysfunction associated with total parenteral nutriation. Dig Dis 1991;9:106-24.  Back to cited text no. 15
    

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Correspondence Address:
Kamel El-Reshaid
Professor, Department of Medicine, Faculty of Medicine, Kuwait University, P. O. Box 24923, 13110 Safat
Kuwait
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DOI: 10.4103/1319-2442.121304

PMID: 24231489

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