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Case Report
ARTICLE IN PRESS
doi:
10.4103/ijn.ijn_137_23

A Case of Neuroleptic Malignant Syndrome–Prompted Myoglobin Cast Nephropathy

Departments of Nephrology, Indira Gandhi Institute of Medical Science, Patna, Bihar, India
Department of Microbiology, All India Institute of Medical Sciences, Patna, Bihar, India
Corresponding Author: Dr. Prem S. Patel, Department of Nephrology, Indira Gandhi Institute of Medical Science, Patna - 800 014, Bihar, India. E-mail: drpspdm@gmail.com
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How to cite this article: Patel PS, Singh PP, Archana, Kumar O. A Case of Neuroleptic Malignant Syndrome– Prompted Myoglobin Cast Nephropathy. Indian J Nephrol. doi: 10.4103/ijn.ijn_137_23

Abstract

Myoglobin cast nephropathy is a sequel of rhabdomyolysis, and is characterized by the release of free myoglobin in the circulation, direct proximal convoluted tubule injury, and obstruction by myoglobin cast in distal tubules. We report an interesting case of myoglobin cast nephropathy in a patient who was on neuroleptic drugs and who presented with neuroleptic malignant syndrome and acute kidney injury.

Keywords

Myoglobin cast nephropathy
myoglobin
neuroleptic malignant syndrome
neuroleptic
pigment nephropathy

Introduction

Rhabdomyolysis is an important cause of pigment nephropathy.1 Neuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic drugs.2 Rhabdomyolysis releases the free myoglobin in circulation, which causes direct proximal convoluted tubule injury and obstruction by myoglobin cast in distal tubules called “myoglobin cast nephropathy”.3 We discuss an interesting case of myoglobin cast nephropathy in a patient was on antipsychotic drugs and presented with fever, rigidity, breathlessness, oliguria, and acute kidney injury.

Case Report

A 48-year man on antipsychotic drugs presented with fever, abnormal tightening and posture of the body, and an episode of transient loss of consciousness over two days. It was not associated with convulsion, incontinence, headache, and visual disturbance. There was no history of diabetes or tuberculosis. He did not give a history of cough, hematuria, lower urinary tract symptoms, diarrhea, or intake of nephrotoxic drugs. He was taking quetiapine (50 mg) twice daily and chlorpromazine (100 mg) once a day for schizophrenia for the last two years. He was admitted to a local hospital and received supportive treatment for three days and was referred to us with complaints of progressive oliguria and anasarca of five days duration. A general examination revealed pallor and anasarca. His blood pressure was 160/90 mmHg, pulse rate 108/min, respiratory rate 24/min, and body temperature 101.8°F. His chest had bilateral crepitation. Cardiovascular and abdominal examinations were normal. Neurological examination was unremarkable, except for disorientation and rigidity of extremities and trunk. Papilledema and sign of meningeal irritation were negative. His urine output was about 100 ml per day. Hemogram was normal. The biochemical result showed serum creatinine at 6.3 mg/dl, elevated LDH (800 IU/L), CPK (9789 IU/L), and serum myoglobin levels (560 ng/ml). CSF analysis, EEG, and MRI brain were normal. A urine dipstick test was positive for blood, without red blood cells on microscopy. Other laboratory reports are mentioned in Table 1. Finally, after obtaining written consent, a kidney biopsy was performed with suspicion of pigment nephropathy. Renal histopathology revealed non-proliferative glomeruli. Segmental sclerosis, tuft necrosis, subendothelial/congophilic deposits, or crescent formation was absent. Tubular atrophy and interstitial fibrosis involved about 10%–12% of sampled cortex. Tubule showed prominent cytoplasmic vacuolar changes and diffuse severe acute injury with epithelial simplification and loss of brush border. A few variably sized, coarse, granular, confluent, variably pigmented cast and focally accompanied by inflammatory cell reaction was seen. Arteries showed medial thickening and subintimal sclerosis. Direct immunofluorescence was negative for the immune complex. The tubular cast was positive for myoglobin and negative for hemoglobin on immunohistochemistry staining. Electron microscopy revealed focal effacement (about 10%) of visceral epithelial cell foot processes. Electron-dense or organized deposits were absent [Figure 1]. The kidney biopsy established the diagnosis of Myoglobin cast nephropathy. A psychiatrist’s advice was sought, neuroleptic drugs were discontinued, oral bromocriptine (2.5 mg) twice a day and trihexyphenidyl (2 mg) daily were started and continued for 2 weeks. He was managed with intravenous fluid, hemodialysis, and symptomatic treatment. He required a total of seven hemodialysis sessions over 2 weeks and his urine output progressively increased. His serum creatinine (0.85 mg/dl) and urine output (approximately 1500–2000 ml/day) normalized by the fourth week.

Table 1: Baseline characteristics of the case at the time of hospitalization
Hematology
Total leucocyte count 8384/mm3 (normal 4010×103/mm3)
Differential leucocyte count N68%/L26%/E2%/M4%
Platelet count 173000/mm3 (normal 150–400×103/mm3)
Hemoglobin 12.6 gm/dl (normal 13–17 g/dl)
ESR 25 mm/hour (normal 0–15 mm/h)
Biochemistry & Serology
Serum creatinine 6.3 mg/dl(normal 0.6–1.3 mg/dl)
Blood urea Nitrogen 41 mg/dl(normal 5–18 mg/dl)
Serum Na+ 133 mmol/L (normal 135–145 mmol/L)
Serum K+ 4.6 mmol/L (normal 3.5–5.5 mmol/L)
Serum Ca2+ 8.5 mg/dl(normal 8.6–10.3 mg/dl)
Serum phosphate 4.3 mg/dl(normal 3.5–4.5 mg/dl)
Serum uric acid 4.8 mg/dl(normal 2.5-7.0 mg/dl)
Serum bilirubin 1.3 mg/dl(normal 0.2–1.0 mg/dl)
ALP 346 U/L (normal <120 U/L)
SGPT 25 IU/L (normal 5×45 IU/L)
SGOT 81 IU/L (normal 5–40 IU/L)
Total serum protein 6.8 gm/dl (normal 6–8 gm/dl)
Serum albumin 3.7 gm/dl (normal 3.5–5.5 gm/dl)
RBS 98 mg/dl(normal <140 mg/dL)
LDH 800 IU/L (normal <248 IU/L)
CPK-MM 9789 IU/L (normal <171 IU/L)
Serum myoglobin 560 ng/ml(normal 28–72 ng/ml)
Serum procalcitonin Negative
HIV/HBsAg/HCV Non-reactive
Urine analysis Albumin-Nil, Blood ++, RBC-2–3/hpf, Pus Cell 6–8/hpf
Immunological markers
ANA, PR3 and MPO ANCA Negative
Complement C3 108 mg/dl (Normal 90–180)
Complement C4 18.1 mg/dl (Normal 10–40)
Radiology
ECG Normal Sinus rhythm
2D ECHO Normal study
USG Abdomen RK10.2 cm, LK 10.0 cm in size, grade I echogenicity, and CMD intact
Microbiology & Pathology
Urine culture No growth
Figure 1:
(a) Tubule showing prominent cytoplasmic vacuolar changes, epithelial simplification, and loss of brush border and diffuse severe acute injury. A few variably sized, coarse, granular (thick yellow arrow), pigmented cast (thin red arrows), and focally accompanied by inflammatory cell reaction. (40×, PAS). (b) The tubular cast was positive for myoglobin (voilet arrows) on immunohistochemistry staining. (40×, IHC).

Discussion

Neuroleptic malignant syndrome (NMS) is an important cause of rhabdomyolysis However, nowadays it is rare, and the incidence has declined from around 0.2%–3.2% to 0.01%–0.02% of patients on antipsychotic drugs.2 This condition develops due to a sudden reduction in dopaminergic neural activity and is characterized by fever, altered sensorium, muscle rigidity, and dysautonomia.2 NMS can lead to severe rhabdomyolysis and renal failure. Characteristic laboratory of NMS includes elevated CPK and leukocytosis. Serum CPK, was elevated in our patient, and is the most sensitive marker of muscle injury.4 Rhabdomyolysis is characterized by the breakdown of striated muscle and the release of myoglobin into circulation.4 Serum myoglobin (560 ng/ml, normal 28–72 ng/ml) was also elevated in our cases. The serum myoglobin levels peak before serum CPK, and its metabolism is rapid and unpredictable. Myoglobin (17.8-kDa) causes renal vasoconstriction, direct injury to the proximal tubule, and after precipitation with the Tamm–Horsfall protein, it forms a myoglobin cast in the distal tubule.3,5 Clinical and biochemical markers suggestive of rhabdomyolysis-associated kidney injury were confirmed on kidney biopsy. NMS is a neurological emergency, and a delay in treatment can potentially lead to serious complications or death. The first step in the treatment of NMS is the cessation of neuroleptic drugs. The next step is the institution of supportive treatment like aggressive hydration to prevent kidney injury, treatment of hyperthermia, and metabolic abnormalities. In severe cases of NMS, empiric therapy with bromocriptine mesylate (dopamine agonist) and dantrolene sodium (muscle relaxant) has been used.6 We managed our case with the cessation of neuroleptic drugs, oral bromocriptine (2.5 mg) twice a day for 14 days, oral trihexyphenidyl (2 mg) daily, intravenous fluid, hemodialysis, and other symptomatic treatment. The renal function and urine output normalized by the fourth week. Hence, timely diagnosis and prompt institution of preventive and therapeutic measures are paramount in managing NMS.

Conclusion

Myoglobin cast nephropathy was caused by rhabdomyolysis secondary to neuroleptic malignant syndrome, probably precipitated by neuroleptic drugs. Thus, reporting a case of myoglobin cast nephropathy could be helpful to clinicians engaged in the management of Neuroleptic Malignant Syndrome.

Acknowledgment

We are thankful to Dr. Alok Sharma, MD, technical director, of Renal Pathology & Transmission electron microscopy, Dr. Lal Path Labs Ltd., for providing histopathology images of the patient.

Informed consent

Informed consent was obtained for the use of data and images in the publication.

Conflicts of interest

There are no conflicts of interest.

Financial support and sponsorship

Nil.

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