Atypical presentation of post infectious glomerulonephritis as malignant hypertension and thrombotic microangiopathy
A 28-year-old male was healthy until one month before admission, when he experienced increasing tiredness and lethargy. Two days before hospitalization, he developed fever, headache with blurring of vision. On the day of admission he had one episode of convulsions and developedaltered sensorium. Clinical examination revealed pallor bilateral pitting pedal edema. Blood pressure was 180/100 mmHg in supine position; heart rate, 96 beats/min; temperature, 101° F; respiratory rate, 32 breaths/min. Neurologic examination suggested postictal confusion with papilloedema, bilateral flexor plantar reflex and no signs of neck stiffness. Lungs showed bibasal rales. Rest of the physical examination was unremarkable. Initial laboratory investigation showed serum creatinine, 3.89 mg/dl; blood urea nitrogen, 84 mg/dl; serum potassium, 4.5 mEq/l; chloride, 99 mmol/l; sodium, 134 mmol/l; white blood cell count, 13600 cells/cumm; hemoglobin, 7.8 gm/dl; platelet count, 90000/cumm; calcium, 8.6 mg/dl; phosphorus, 3.5 mg/dl; albumin, 3.6 gm/dl; bilirubin 0.9 mg/dl; serum iron, 20 μmol/l and lactate dehydrogenase(LDH), 1280 U/l. Urinanalysis showed specific gravity 1.025, pH 6.0, 4+ protein, 15-20 pus cells/hpf, 25-30 red blood cells (RBCs)/hpf and 1-2 granular casts. 24 h urine protein leak was 1.9 g/d. Liver function test, lipid profile and thyroid function tests were within normal limits. On ultrasonography - both kidneys were of normal size, but with increased parenchymal echogenicity. Computed tomography scan of head revealed ill-defined hypodensities at bilateral parieto-occipital region consistent with posterior reversible encephalopathy syndrome. Because of the complex clinical syndrome (hypertensive encephalopathy syndrome coupled with proteinuria and active urine sediments), a percutaneous renal biopsy was performed. Serologic tests were negative for anti-streptolysin-O antibody titre, antinuclear antibody, anti-double stranded deoxyribonucleic acid antibody, anti-neutrophil cytoplasmic antibodies profile by ELISA and anti-glomerular basement membrane antibody. Serum complement levels (C3, C4) were normal. Screening for hepatitis B, hepatitis C and human immunodeficiency virus was negative. On light microscopy, there were twenty two viable glomeruli displaying two pathologies simultaneously. Majority of them appeared solid and proliferative comprising neutrophilic infiltration in the capillary tufts obliterating capillary lumen secondary to proliferation of endothelial cells, neutrophils and sparse mesangial cells; with single contoured basement membranes []. Two of these glomeruli (9%) possessed circumferential oriented active cellular crescents, without necrotizing lesions []. Lobular accentuation was absent. In addition, five glomeruli (devoid of neutrophilic infiltration) showed changes of TMS in the form of blood filled, engorged capillaries [], and fibrin thrombus in the hilar arteriole. Mesangiolysis was noted. Moderate degree of acute tubular injury was noticed with fresh RBC's in the lumen. There was no focus of tubular atrophy/interstitial fibrosis. Interstitium lacked inflammation or granuloma. Artery and arterioles showed hypertensive changes to a moderate extent in the form of hypertrophic muscular wall and intimal thickening. Marked intimal hyalinosis was present in smaller arterioles. Fibrinoid necrosis of vessel wall, luminal thrombosis or vasculitis was not evident. Immunofluorescence revealed diffuse and global, coarse granular deposits along the capillary walls and mesangium with C3 (3+) and IgG (2+) in five available glomeruli []. Kappa and lambda light chain stains showed 2+ positivity in a similar pattern. C3 deposits were also seen in vessels. IgA, IgM and C1q were negative. A diagnosis of coexistent TMA and APIGN with focal (9%) crescents was established. Upon probing, patient denied any symptom of previous infective episode.\nPatient was treated with intravenous antibiotics, intravenous pulse methyl prednisolone (1 g for 3 days) considering the presence of active crescents histologically, followed by tapering dose of oral prednisolone; along with strict control of blood pressure. He was treated with intravenous nitroglycerine infusion during the early phase of the disease, followed by oral ramipril 5 mg twice daily, clonidine 0.1 mg thrice daily, frusemide 40 mg thrice daily, metalozone 5 mg twice daily and prazocin 5 mg twice daily. There was a dramatic improvement in his renal function with decrease in serum creatinine (1.5 mg/dl) as well as trace proteinuria. TMA was also resolved as evidenced by normalization of serum LDH level, hemoglobin and platelet count.