An 82 year old Caucasian female was admitted to our hospital in April 2008 with pitting edema of her legs arms and back. Her past medical history was significant for an appendectomy at the age of 29 years, a hyster- and ovariectomy at the age of 50 years, as well as status post varicose stripping, bilateral knee arthrosis, hypercholesterolemia and a reported diphtheria infection as a child. No history of allergic diseases or malignoma was present. Her regular medication consisted of low dose acetylsalicylic acid (100 mg/d), simvastatine (5 mg/d) and occasionally diclofenac (about 3 times a year, last time four months prior to admission). The outpatient nephrologist started medical therapy with spironolactone (25 mg) and furosemide (up to 400 mg/d) three days prior to admission. Laboratory data from her routine outpatient visits showed no proteinuria as well as normal renal function until January 2007.
On January 17th 2008, the patient received a combined intramuscular vaccination for tetanus, diphtheria and poliomyelitis (REVAXIS, Sanofi Pasteur MSD GmbH, Leimen, Germany), as her last vaccination for tetanus had been performed in April 1998. The vaccination was composed of cleaned tetanus toxoid, cleaned diphtheria toxoid, inactive poliomyelitis virus Typ 1–3, aluminiumhydroxide, 2-Phenoxyethanol, formaldehyde, medium 199 (mixture of aminoacids, minerals, vitamins, polysorbat 80) and trace amounts of neomycin, streptomycin and polymyxin B. No local vaccination reaction occurred after injection. At the end of February slight leg edema occurred. The general practitioner performed echocardiography for suspected heart failure. As the echocardiography revealed only mild aortic-valve-insufficiency and mild mitral valve-insufficiancy, with an intact overall contractility this diagnosis was dismissed. Meanwhile the edema worsened constantly, impressively indicated by an increase in bodyweight from 72 kg to 84 kg in one month. Moreover, the previous normotensive patient became hypertensive with blood pressure of 186/101 mmHg. Urinary dip-stick analysis now showed massive (+++) proteinuria on which the patient was transferred to a nephrologist. The 24 hours collected urine showed massive unselective proteinuria (12 g/day), therapy with spironolactone and furosemide failed to alleviate the edematous state. The urine sediment revealed multiple erythrocyte cylinders on which the patient was transferred to our tertiary care hospital for further nephrological evaluation and treatment. Upon admission physical examination was significant for general edema and multiple localised makulopapulous exanthema of the feet and legs. Vital parameters were unremarkable. The chest radiograph showed no signs of pleural effusions or malignancies. Laboratory tests revealed unselective nephrotic proteinuria (7.13 g/d), hypoproteinemia (47 g/l) and hypercholesterolemia (605 mg/dl). Serum creatinine was 74 μmol/l. The 24 hour collected urine revealed a reduced creatinine-clearance of 46 ml/min. Urinary sediment showed mild microhaematuria (5–10 erythrocytes/μl) and a few granulated and hyaline cylinders but no signs of an active sediment. Analysis for antinuclear antibodies, ANCA, antibodies against double-strain-DNS, anti-GBM-antibodies and Hepatitis B and C were negative or within normal limits. The kidneys were of normal size but showed bilateral mild enhancement in the abdominal ultrasound. Further diagnostic workup showed no evidence of malignancies.
Renal biopsy was performed and showed typical minimal change lesion without evidence of focal and segmental glomerulosclerosis (Figure 1). Three of the 22 glomerula showed globalsclerosis, minimal tubulo-atrophie and interstitial fibrosis (< 5% of the cortex). Further immunological staining excluded mesangial and glomerular IgM, IgA, IgG, C3 or fibrin/fibrinogen deposits.
After minimal change diagnosis was assured by biopsy, therapy with steroids (1 mg/kg body weight/day) and an ACE-inhibitor (ramipril 5 mg/d) was initiated. After ten days of therapy with steroids (75 mg/d) with concomitant oral phenprocourmon the nephrotic range proteinuria reduced to 1.17 g/24 h (Figure 2). On the last follow-up in the end of April 2009 serum-creatinine fell to 62 μmol/l, the blood pressure normalized and proteinuria was not detectable in a 24 h urine collection.