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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 4  |  Page : 636-642
Primary HIV Infection Presenting as Non-traumatic Rhabdomyolysis with Acute Renal Failure

Department of Nephrology, Sri Ramachandra Medical College, Sri Ramachandra University, Chennai, Tamil Nadu, India

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Renal disease is a relatively common complication in patients infected with the human immunodeficiency virus (HIV). A collapsing form of focal glomerulosclerosis has been considered as the primary form of HIV nephropathy. HIV infection is also associated with an increasing number of different forms of renal disease. Acute renal failure (ARF) syndromes are frequently noted during the course of HIV infection. The most common include the following: acute and often reversible renal failure resulting from infection, hypotension, and administration of nephrotoxins used to treat opportunistic infections, and the use of highly active anti-retroviral therapy. ARF has been reported in up to 20% of hospitalized HIV infected patients compared to 3 to 5% of non-HIV infected patients. Primary HIV in-fection is usually symptomatic, and infected patients can present with a variety of symp-toms. Although ARF syndromes are frequently noted during the course of infection, it is an uncommon presentation of primary HIV infection. We describe a 42-year-old man who presented at our hospital with acute self-limited rhabdomyolysis and who was found to have primary HIV infection. Our case and other reports suggest that a diagnosis of primary HIV infection needs to be considered in patients who present with acute rhabdomyolysis.

Keywords: HIV, Rhabdomyolysis, Acute renal failure

How to cite this article:
Prabahar MR, Jain M, Chandrasekaran V, Indhumathi E, Soundararajan P. Primary HIV Infection Presenting as Non-traumatic Rhabdomyolysis with Acute Renal Failure. Saudi J Kidney Dis Transpl 2008;19:636-42

How to cite this URL:
Prabahar MR, Jain M, Chandrasekaran V, Indhumathi E, Soundararajan P. Primary HIV Infection Presenting as Non-traumatic Rhabdomyolysis with Acute Renal Failure. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2022 Dec 2];19:636-42. Available from: https://www.sjkdt.org/text.asp?2008/19/4/636/41328

   Introduction Top

Renal disease is a relatively common com­plication in patients infected with the human immunodeficiency virus (HIV). A collapsing form of focal glomerulosclerosis has been con­sidered as the primary form of HIV nephro­pathy. [1] HIV infection is also associated with an increasing number of different forms of renal disease. Acute renal failure (ARF) is frequently noted during the course of HIV infection and has been reported in up to 20% of hospitalized HIV infected patients compared to 3 to 5% of non-HIV infected patients. [2] Acute renal failure in HIV pa­tients is most commonly pre-renal azotemia or acute tubular necrosis (ATN) due to dia­rrheal diseases, infection, septicemia, bleeding, hypoalbuminemia, or nephrotoxins. [3] Recent studies highlight an increased incidence of HIV associated thrombotic microangiopathies and rhabdomyolysis, the latter from the use of statins in combination with highly active anti-retroviral therapy (HAART). [4],[5],[6],[7] Post renal ARF due to tumor, lymph nodes, retrope­ritoneal fibrosis, or crystalluria due to indi­navir, acyclovir, or sulphadiazine is rare. [8] Renal biopsies in patients of severe ARF (when pre-renal or ATN was not suspected) have shown hemolytic uremic syndrome in 53%, ATN in 40%, obstructive renal failure due to crystalluria in 26%, HIV-associated nephropathy (HIVAN) in 23%, acute inters­titial nephritis in 3%, and various other glomerulopathies in 6%. [9]

Although ARF is frequently noted during the course of HIV infection, it is an un­common presentation of primary HIV in­fection. We herein report a 42-year-old man who presented at our hospital with acute self­limited rhabdomyolysis and who was found to have primary HIV infection.

   Case report Top

A 42-year-old man presented to our emer­gency department with persistent leg pain, vomiting, shortness of breath and high colored urine. One week prior to admission, he began to experience diffuse pain in the back, the posterior muscle groups of both thighs and the calf muscles. The pains per­sisted as a dull aching sensation that wor­sened with activity. There was no history of trauma or heavy physical exertion. He denied having fever, fatigue, weakness, or weight loss. The patient's past medical history was not significant. He was not taking either prescribed or over-the-counter medications. He denied that he smoked tobacco, but did inform us that he consumes alcohol occa­sionally. He last drank alcohol a month ago. He denied having any history of high-risk sexual behavior or injection drug use. He worked as a sales executive. There was no known inhaled or ingested toxin exposure. Physical examination revealed bilateral in­guinal lymphadenopathy and pedal edema, but the results of his physical examination were otherwise unremarkable. Of note, there was no muscle tenderness, and the muscle power was 5/5 in all his extremities. There was no neurologic deficit.

Laboratory investigations revealed the fo­llowing values: His serum creatinine was 6.8 mg/dl. The serum phosphorus, calcium and uric acid levels were 14 mg/dl, 4.7 mg/dl, and 17mg/dl respectively. His urine dipstick for blood was positive and he had 4+ pro­teinuria; microscopy revealed numerous gra­nular casts, no epithelial cells, and no red blood cells (RBCs). Since the patient had red urine and no RBCs in the urine, test for urine myoglobin was done which was found to be positive. Levels of creatine phospho­kinase (CK) and CK-MB were done which were 2,78,000 IU/L with an MB fraction of 678 ng/mL. The results of urine and serum toxicology screening were negative. Liver function tests showed aspartate aminotrans­ferase level of 3640 U/L and alanine amino­transferase of 419 U/L. The total bilirubin, alkaline phosphatase, total protein, and al­bumin levels were all within normal limits. His anti-streptolysin O (ASO) titer, C3, C4 complement levels were within normal limits and the erythrocyte sedimentation rate was 7 mm/hr. The results of antinuclear antibody and anti-JO-1 antibody tests were negative. Cultures of blood samples tested negative, and purified protein derivative skin test was non-reactive. X-rays of the chest and lower extremity as well as electrocardiogram did not reveal any abnormality. Nerve conduc­tion and electromyographic studies showed no evidence of muscle pathology. Based on clinical examination and the laboratory para­meters the patient was diagnosed to have ARF due to rhabdomyolysis.

An HIV ELISA done as a routine pre­dialysis serology screening after obtaining in­formed consent, was found to be reactive. He was dialyzed through right internal ju­gular catheter as he had uremic symptoms, oligoanuria and fluid overload. Kidney biop­sy was done under ultrasound guidance, which showed congested glomeruli, inters­titial infiltrates, acute tubular necrosis (ATN) and intra tubular casts [Figure 1]. His plasma HIV RNA level was positive at 6,38,000 copies/mL and CD4 count was 436 cells/ mm 3 . He had no other opportunistic infec­tions or other HIV-related illnesses. The patient was tested for other viral illnesses.

Serological tests for hepatitis B, hepatitis C, cytomegalovirus (CMV) and Ebstein barr virus (EBV) were negative. Six days after admission, the patient's leg pain resolved and his CK level fell to 623 IU/ L. His urine output gradually increased and serum crea­tinine level normalized (0.7 mg/dl) after two weeks. The result of a repeat ELISA for HIV antibody performed one month after discharge was positive, as was the result of a western blot assay; the plasma HIV RNA level at that time was 2,62,800 copies/ml and CD4 count was 286 cells/mm 3 . He has been followed-up for more than one month since his hospitalization, and he has had no recurrence of symptoms, despite his decision to decline anti-retroviral treatment.

   Discussion Top

The term rhabdomyolysis refers to disin­tegration of striated muscle, which results in the release of muscular cell constituents into the extra cellular fluid and the circula­tion. One of the key compounds released is myoglobin, an 18,800-Dalton oxygen carrier. Normally, myoglobin is loosely bound to plasma globulins and only small amounts reach the urine. When massive amounts of myoglobin are released, the binding capacity of the plasma protein is exceeded. Myo­globin is then filtered by the glomeruli and reaches the tubules, where it may cause obstruction and renal dysfunction. [10]

The severity of illness ranges from asymp­tomatic elevations of muscle enzymes in the serum to life-threatening cases associated with interstitial and muscle cell edema, con­traction of intravascular volume, extreme en­zyme elevations, electrolyte imbalances, and pigment-induced ARF. One major cause of rhabdomyolysis is the crush syndrome, i.e., myolysis linked to traumatic compression of muscle followed by reperfusion, as is frequently seen in accidents or disasters. [11] Non-traumatic causes of rhabdomyolysis include heritable muscle enzyme deficiencies, electrolyte abnormalities, infections, drugs, toxins, and endocrinopathies. [12]

Rhabdomyolysis was observed even in ancient times. [13] The Old Testament refers to a plague suffered by the Israelis after consumption of quail. Myolysis after the consumption of quail is the result of intoxication by hemlock herbs, which are consumed by quails during their spring migration. In modern times, the first cases of crush syndrome and ARF were reported during the Sicilian earthquake in Messina in 1908 and in the German military medical literature during World War I. [14] But it was only decades later, in the early 1970s, that non-traumatic causes of rhabdomyolysis were recognized and identified as a potential cause of ARF. [12]

The classic presentation of rhabdomyolysis includes myalgias and myoglobinuria in association with elevated serum muscle enzymes. [13] In many cases, however, pigmenturia may be overlooked because the filtered load of myoglobin is insufficient to produce grossly pigmented urine or has resolved before the patient seeks medical attention. Myoglobin is cleared from the serum more rapidly than CK, so that it is not unusual for serum CK levels to remain elevated in the absence of myoglobinuria. [15] The hallmark of rhabdomyolysis is an elevation of serum muscle enzymes. Serum CK levels may be massively elevated to above 100,000 IU/L. The CK is entirely or almost entirely of the MM or skeletal muscle fraction, although small amounts of the MB or myocardial fraction may be present. The presence of MB reflects the small amount found in skeletal muscle rather than the presence of myocardial disease. Elevation of serum aminotransferase enzymes due to muscle damage is frequent and can cause onfusion if attributed to liver disease. Although serum CK also rises with myocardial infarction, patients with rhabdomyolysis alone have no detectable rise in serum troponins and do not have ischemic chest pain or ECG signs of myocardial infarction

Primary HIV infection, or "acute retroviral syndrome," is increasingly recognized as a clinical syndrome with a wide variety of presentations. Primary HIV infection appears to be symptomatic in most cases, but it is often unrecognized. [16] This syndrome typically occurs 2-6 weeks after exposure to HIV and it can present in a variety of ways: from a mild flu like illness to a more severe constellation of complaints, including fever, fatigue, sore throat, anorexia, headaches, myalgias or arthralgias, nausea, cervical adenopathy, diarrhea, or rash .[16],[17] Photophobia, hepatosplenomegaly, and oral thrush have been reported, albeit with less frequency. Laboratory data often reveal thrombocytopenia, lymphopenia, and elevated hepatic transaminase levels. [17] Neurological complications such as aseptic meningitis, peripheral neuropathy, Guillian-Barre syndrome and facial nerve palsies as well as opportunistic infections including toxoplasmosis, esophageal candidiasis, and pneumocystis pneumonia have also been reported in association with acute HIV infection. [18]

Patients with rhabdomyolysis are at all stages of HIV infection and could be classified into three groups:

  1. HIV associated rhabdomyolysis including rhabdomyolysis in primary HIV infection,recurrent rhabdomyolysis, and isolated rhabdomyolysis;
  2. rhabdomyolysis induced by drugs; and
  3. rhabdomyolysis at the end stage of acquired immunodeficiency syndrome including opportunistic infections of muscle and rhabdomyolysis without a definite cause. [19]

In a search of the literature, we were able to find six previous reports of rhabdo­myolysis that occurred in patients with pri­mary HIV infection. [19,][20],[21],[22],[23],[24] In two of these cases, the patients had co-infection with CMV. [22],[23] Chariot and colleagues [25] des­cribed a series of cases in which patients who presented with rhabdomyolysis were HIV seropositive. Twenty patients in total were examined, and three of these were found to have primary HIV infection as the cause of the rhabdomyolysis. The other cases described were related to other compli­cations of HIV infection, such as oppor­tunistic infections and drug-induced rhabdo­myolysis. Rastegar and associates [19] also described rhabdomyolysis in a patient with primary HIV infection. Our case is similar to these reports in several ways. Our case is unique in that our patient presented with acute rhabdomyolysis in the absence of other symptoms that would suggest primary HIV infection. The patients in the previous reports had other symptoms, including sore throat, [20],[21],[23],[24] abdominal pain, [20],[24] and dia­rrhea. [22],[24] In addition, the diagnosis was es­tablished in these other case studies through detection of HIV p24 antigen; whereas we established the diagnosis by western blot analysis and measurement of the HIV RNA level by means of PCR analysis.

Acute rhabdomyolysis has also been des­cribed in patients who are in the later stages of HIV disease, [25] and it has been associated with a number of other acute viral infec­tions, including influenza, coxsackie viruses and epstein-barr virus. [26] The role of HIV and other viruses in rhabdomyolysis is un­known, but it is likely due to an immune­ mediated process. [25]

The pathophysiology of myoglobinuric ARF has been studied extensively in the animal model of glycerol-induced ARF. The main pathophysiologic mechanisms are renal vaso­constriction, intraluminal cast formation, and direct heme-protein induced cytotoxicity. [10] Myoglobin is easily filtered through the glomerular basement membrane. Water is progressively reabsorbed in the tubules, and the concentration of myoglobin rises pro­portionally, until it precipitates and causes obstructive cast formation. Dehydration and renal vasoconstriction, which decrease tubular flow and enhance water reabsorption, favor this process. [10] The high rates of generation and urinary excretion of uric acid further contribute to tubular obstruction by uric acid casts. Another factor favoring precipitation of myoglobin and uric acid is a low pH of tubular urine, which is common because of underlying acidosis. The degradation of intra­tubular myoglobin results in the release of free iron, which catalyzes free radical pro­duction and further enhances ischemic da­mage. [10] Even without invoking release of free iron, the heme center of myoglobin will ini­tiate lipid peroxidation and renal injury. [27] Alkaline conditions prevent this effect by stabilizing the reactive ferryl myoglobin com­plex.

The management of patients with rhabdo­myolysis involves treatment of the under­lying illness and measures to prevent or manage ARF due to myoglobinuria. Saline resuscitation followed, once volume reple­tion has been attained, by forced mannitol­alkaline diuresis (to maintain the urine pH above 6.5) is a widely used approach. Once ARF is established, or severe hyperkalemia and acidosis are present, the patient requires dialysis. Peritoneal dialysis is difficult to admi­nister in patients with abdominal trauma and often is insufficient for the removal of pota­ssium and other catabolic metabolites. Remo­val of myoglobin by plasma exchange has no demonstrated benefit and also is deba­table, because the metabolic turnover of myoglobin is fast. [11]

In summary, our case and others suggest that patients with primary HIV infection can present with acute rhabdomyolysis, and that a diagnosis of primary HIV infection should be considered when a patient presents with rhabdomyolysis, even if there are no appa­rent risk factors.

   References Top

1.Williams DI, Williams DJ, Williams IG, Unwin RJ, Griffiths MH, Miller RF. Presentation, pathology and outcome of HIV associated renal disease in a specialist centre for HIV/AIDS. Sex Transm Inf 1998;74(3):179-84.  Back to cited text no. 1    
2.Valeri A, Neusy AJ. Acute and chronic renal disease in hospitalized AIDS patients. Clin Nephrol 1991;35(3):110-8.  Back to cited text no. 2    
3.Rao TK. Acute renal failure in human immunodeficiency virus infection. Semin Nephrol 1998;18(4):378-95.  Back to cited text no. 3    
4.Perazella MA. Acute renal failure in HIV­infected patients: a brief review of common causes. Am J Med Sci 2000;319(6):385-91.  Back to cited text no. 4    
5.Joshi MK, Liu HH. Acute rhabdomyolysis and renal failure in HIV-infected patients: risk factors, presentation, and pathophysiology. AIDS Patient Care STDS 2000;14(10):541-8.  Back to cited text no. 5    
6.Hare CB, Vu MP, Grunfeld C, Lampiris HW. Simvastatin-nelfinavir interaction implicated in rhabdomyolysis and death. Clin Infect Dis 2002;35(10):e111-2.  Back to cited text no. 6    
7.Alpers CE. Light at the end of the TUNEL: HIV-associated thrombotic microangiopathy. Kidney Int 2003;63(1):385-96.  Back to cited text no. 7    
8.Kopp JB, Miller KD, Mican JA, et al. Crystalluria and urinary tract abnormalities associated with indinavir. Ann Intern Med 1997;127(2):119-25.  Back to cited text no. 8    
9.Ifudu O, Mayers JD, Mathew JJ, et al. Uraemia therapy in patients with end-stage renal disease and human immunodeficiency virus infection: Has the outcome changed in the 1990s? Am J Kidney Dis 1997;29(4): 549-52.  Back to cited text no. 9    
10.Zager RA. Rhabdomyolysis and myohemo­globinuric acute renal failure. Kidney Int 1996;49(2):314-26.  Back to cited text no. 10    
11.Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol 2000;11(8):1553-61.  Back to cited text no. 11    
12.Koffler A, Friedler RM, Massry SG. Acute renal failure due to nontraumatic rhabdo­myolysis. Ann Intern Med 1976;85(1):23-8.  Back to cited text no. 12    
13.Rutecki GW, Ognibene AJ, Geib JD. Rhab­domyolysis in antiquity: From ancient descriptions to scientific explanation. Pharos Alpha Omega Alpha Honor Med Soc 1998;61(2):18-22.  Back to cited text no. 13    
14.Bywaters EG, Beall D. Crush injuries with impairment of renal function. Br Med J 1941;1:427-32.  Back to cited text no. 14    
15.Rizzi D, Basile C, Di Maggio A, et al. Clinical spectrum of accidental hemlock poisoning: Neurotoxic manifestations, rhab­domyolysis and acute tubular necrosis. Nephrol Dial Transplant 1991;6(12):939-43.  Back to cited text no. 15    
16.Schacker T, Collier AC, Hughes J, Shea T, Corey L. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med 1996;125(4):257-64.  Back to cited text no. 16    
17.Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med 1998;339(1):33-9.  Back to cited text no. 17    
18.Russell ND, Sepkowitz KA. Primary HIV infection: Clinical, immunologic, and virologic predictors of progression. AIDS Reader 1998;8:164-72.  Back to cited text no. 18    
19.Rastegar DA, Claiborne CV, Fleisher AS, Matsumoto AK. A patient with primary human immunodeficiency virus infection who presented with acute rhabdomyolysis Clin Infect Dis 2001;32(3):502-4.  Back to cited text no. 19    
20.Mahe A, Bruet A, Chabin E, Fendler JP. Acute rhabdomyolysis coincident with primary HIV-1 infection. Lancet 1989;2 (8677):1454-5.  Back to cited text no. 20    
21.Del Rio C, Soffer O, Widell JL, Judd RL, Slade BA. Acute human immunodeficiency virus infection temporally associated with rhabdomyolysis, acute renal failure, and nephrosis. Rev Infect Dis 1990;12(2):282-5.  Back to cited text no. 21    
22.Schindler JM, Neftel KA. Simultaneous primary infection with HIV and CMV leading to severe pancytopenia, hepatitis, nephritis, perimyocarditis, myositis, and alopecia totalis. Klin Wochenschr 1990;68 (4):237-40.  Back to cited text no. 22    
23.Ragnaud JM, Tahbaz A, Buisson M, et al. Primary coinfection with human immuno­deficiency virus and cytomegalovirus pre­senting as acute rhabdomyolysis. Clin Infect Dis 1995;20(4):1077-8.  Back to cited text no. 23    
24.Guillaume MP, Van Beers D, Delforge ML, Devriendt J, Cogan E. Primary human immunodeficiency virus infection presenting as myocarditis and rhabdomyolysis. Clin Infect Dis 1995;21(2):451-2.  Back to cited text no. 24    
25.Chariot P, Ruet E, Authier FJ, Levy Y, Gherardi R. Acute rhabdomyolysis in patients infected by human immunodefi­ciency virus. Neurology 1994;44(9):1692-6.  Back to cited text no. 25    
26.Singh U, Scheld WM. Infectious etiologies of rhabdomyolysis: 3 case reports and review. Clin Infect Dis 1996;22(4):642-9.  Back to cited text no. 26    
27.Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: The role of myoglobin. Exp Nephrol 2000;8(2):72-6.  Back to cited text no. 27    

Correspondence Address:
Murugesan Ram Prabahar
Department of Nephrology, Sri Ramachandra Medical College, Sri Ramachandra University, Chennai-116, Tamilnadu
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Source of Support: None, Conflict of Interest: None

PMID: 18580027

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