Pancreatorenal syndrome associated with combination antiretroviral therapy in HIV infection

Acute renal failure is an unusual complication of acute pancreatitis, occurring as an isolated event in only 2–4% of cases. Unlike the well-known hepatorenal syndrome, pancreatorenal syndrome is poorly characterised, and the mortality rate is as high as 75–80%. We describe two cases of pancreatorenal syndrome associated with combination antiretroviral therapy for HIV infection. A 47-year-old man was admitted to hospital with fever and increasing abdominal pain. He had been HIV-positive for 6 years with a recent CD4 T-cell count of 31 cells/ L and a viral load of 121 000 copies/mL. He had been treated with combinations of zidovudine, lamivudine, saquinavir, and indinavir until 2 months before admission, when he discontinued antiretroviral therapy. 3 weeks before admission he restarted combination therapy with stavudine (80 mg daily), lamivudine (300 mg daily), and incremental ritonavir. His blood urea nitrogen (BUN) and creatinine were normal. His other medications were azithromycin, ethambutol, dapsone, fluconazole, acyclovir, mexiletene, erythropoietin, and testosterone. The symptoms that prompted admission occurred when he began taking fulldose ritonavir (1200 mg daily). He weighed 66 kg. Tests showed amylase 843 U/L (normal 45–130), lipase 200 U/L (normal 5–30), and triglycerides 20·9 mmol/L (normal 0·5–1·8). The BUN was 20·7 mmol/L (normal 1·8–8·9) and creatinine 344·8 mol/L (normal 26·5–123·8). Computed tomography (CT) scan of the abdomen revealed phlegmonous pancreatitis without gallstones or renal calculi. Multiple cultures for bacteria, fungi, and acid-fast bacilli were negative, and stool examination was unremarkable. Antiretroviral drugs were discontinued. Subsequently the patient developed nausea and vomiting, and the BUN and creatinine rose to 41·8 mmol/L and 760·2 mol/L over the next 4 days. Urinalysis showed a specific gravity of 1·025 (normal 1·005–1·025) with trace proteinuria and coarse granular casts. A repeat CT scan showed persistent pancreatic inflammation. Dialysis was initiated, but the BUN and creatinine rose to 68·5 mmol/L and 1096·2 mol/L and the patient developed severe metabolic acidosis with a serum carbon dioxide of 12·5 mmol/L (normal 24–31). Dialysis was continued during the next 16 days, and he gradually improved. He was discharged after 6 weeks with a normal amylase and normal renal function. A 40-year-old man was admitted to hospital with fever, abdominal pain, and increasing abdominal girth. He had been HIV-positive for 12 years and had taken zidovudine, didanosine, and zalcitabine sequentially. 10 months before admission his CD4 count was 12 cells/ L and his plasma viral load was 1·1 million copies/mL, and he began combination antiretroviral therapy with lamivudine (300 mg in four of eight cases with autism at necropsy (ages 4–33 years). Enlarged brains have also been documented in individuals with autism studied by magnetic resonance imaging. We studied the association between macrocephaly and autism in South Carolina. Families of all individuals younger than 21 years who receive services for autism from South Carolina were eligible to participate in this study. Enrolment was voluntary. Other characteristics of the study population included: mean age 8 years, 12% with height above 97th centile, 20% with weight above 97th centile, 5:1 male/female ratio, mean maternal age 28 years (range 15–44), mean paternal age 29 years (range 19–53), and mean birth order 2·2. A specific genetic diagnosis was found in 8% of cases. Cognitive function was similar in the macrocephalic and non-macrocephalic individuals (means for IQ 51 and 50, respectively), but adaptive function was lower in macrocephalic individuals (means for Vineland Scale 40 and 49, respectively). Autism was confirmed by the Autism Diagnostic Interview, Revised, or the Childhood Autism Rating Scale in all participants with macrocephaly. Macrocephaly appears to be the single most consistent physical characteristic of children with autism. The head circumference was greater than 2 SD above the mean for age and sex in 24% of the first 100 individuals under 21 years enrolled in the South Carolina (USA) Autism Study. By contrast, only 3% had microcephaly (head circumference less than 2 SD below the mean). 80% of the study participants had head circumferences above the mean. Birth head circumferences were available for 18 of the 24 individuals with macrocephaly. The head size at birth was normal in all except one of these 18 individuals (figure). One or both parents of 62% of the individuals with macrocephaly also had macrocephaly. Magnetic resonance imaging in four cases showed no evidence of structural anomalies or ventricular enlargement. Macrocephaly may represent a clinical marker for grouping individuals with autism into more homogeneous subgroups. Such subgroups may be useful for genetic linkage analysis and in the search for candidate genes which cause or predispose to autism.