A 23-year-old man presented to hospital with a 2-week history of oedema, frothy urine and lower abdominal pain. This is on a background of ulcerative colitis (UC) for which he was on sulfasalazine. He denied any other regular medications, over the counter medications or herbal supplements. His family history included his mother having IgA nephropathy. He was an occasional smoker and rarely consumed alcohol. He denied illicit drug use. On examination, he was mildly tachycardic (105 beats per minute) and normotensive. He was 180 cm tall and weighed 93 kg. He had mild bilateral pitting oedema to his knees. The rest of his examination was unremarkable. Investigations revealed normal renal function with a creatinine of 75 μmol/L, hypoalbuminaemia with a serum albumin of 15 g/l and urinalysis revealing 3+ protein. His urinary albumin to creatinine ratio (uACR) was 944.9 mg/mmol. His total cholesterol was 8.3 mmol/L. GN, vasculitis, infection and myeloma screen (dsDNA, C3 & C4, anti-PLA-2R, hepatitis B & C serology, serum free light chains and serum protein electrophoresis with immunofixation) were negative, with the exception of a positive atypical perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). Importantly the myeloperoxidase (MPO) and proteinase 3 (PR3) titres were both < 1 IU/ml. ANCA positivity is most likely explained by our patient’s history of UC where ANCA positivity is reported in 60–80% of patients, with a predominant p-ANCA pattern [].
During preparation for renal biopsy our patient was found to have a prolonged activated partial thromboplastin time (aPTT) of 47 s. This corrected on a mixing study. Factor 12 deficiency (29%) was subsequently identified. Haematology opinion was that this conferred no increase in in vivo bleeding risk.
Renal biopsy was undertaken with LM revealing no morphological abnormality (see Fig. ). IF revealed nonspecific trace glomerular deposits of IgM and C3. MCD was the most likely diagnosis. Our patient was consequently commenced on 75 mg oral prednisone daily.
After 1 month our patient achieved complete remission. He was no longer oedematous, his serum albumin was 33 g/l (from 15 g/L) and uACR was 0.7 mg/mmol (from 944.9 mg/mmol). His prednisone was slowly weaned from 75 mg daily to 50 mg daily for a fortnight and then 25 mg daily for a fortnight. Our patient remained in remission with a serum albumin of 39 g/L, total cholesterol of 6 mmol/L and no albuminuria.
The electron microscopy (EM) report from our patient’s renal biopsy returned 2 months later. This revealed patchy foot process effacement, and mesangial expansion with some deposits suggestive of a mesangiopathic process (see Fig. ).
Our patient then suffered a dramatic relapse with the prednisone dose at 20 mg/day. He reported recurrence of frothy urine, 4 kg of weight gain and proteinuria (on urine dipstick given for home monitoring). His prednisone was increased to 25 mg daily but despite this his oedema worsened and proteinuria persisted. Therefore his prednisone dose was further increased to 75 mg daily to induce remission (see Fig. ).
A complete clinical remission was achieved over the next 2 months with serum albumin improving to 38 g/L and total cholesterol to 6.3 mmol/L. At this stage he was commenced on oral cyclosporin 100 mg BD as a steroid sparing agent given the previous failed attempt to wean steroids. Over the next 5 months our patient’s prednisone dosage was weaned more slowly. At a dose of 10 mg prednisone daily he suffered a second relapse with recurrence of oedema in association with albuminuria and hypoalbuminaemia to his previous levels. His prednisone dose was increased back to 50 mg daily and then 75 mg daily to re-induce remission.
Given his multiple relapses, steroid dependence and initial EM report suggestive of a mesangiopathic process, our patient underwent a second renal biopsy. LM was again normal, however IF found significant mesangial deposits of IgM (2–3+) and C3 (2–3+) (see Figs. and ). IgM nephropathy was then consider a possible diagnosis.
This time our patient took longer to achieve remission, requiring 75 mg prednisone daily and an increase in his cyclosporin dose to 125 mg BD. His prednisone dose was again weaned to 25 mg daily. He also self-ceased his cyclosporin. Our patient was adherent to the recommended prednisone dose as he recognised that without it he would relapse, and he felt further relapses would impact his career progression.
After more than 12 months on prednisone 25 mg daily, and a total of 2 years on continuous corticosteroids, our patient agreed to a slow wean of the corticosteroid dose. Our plan was to use anti-human CD20 (Rituximab) if severe nephrosis recurred. He once again relapsed as soon as his prednisone dose reached 20 mg daily. At this stage his prednisone was increased to 50 mg daily, and he received the first of two planned doses of Rituximab 1 g as an outpatient. He suffered no adverse reactions from the rituximab. During this relapse, his serum albumin reached 10 g/L, 24 h urinary protein was 14.76 g/day and his total cholesterol was 11.5 mmol/L (see Fig. ).
Several days after the rituximab infusion, our patient presented to the Emergency Department with a severe headache, nausea and vomiting. His headache had been progressively worsening since the day prior to his rituximab infusion. There were no focal neurological signs on examination. Computed tomography brain (CTB) and computed tomography angiogram (CTA) revealed a right transverse sinus thrombosis and non-occlusive posterior sagittal sinus thrombosis. We found no evidence of any inherited or acquired thrombophilia with extensive testing (anti-thrombin 3, factor V Leiden, lupus anticoagulant, prothrombin gene mutation, protein C & S, JAK 2 mutation analysis and paroxysmal nocturnal haemoglobinuria assay). He was commenced on therapeutic enoxaparin and bridged to warfarin.
He went on to receive a second dose of rituximab 1-month later. Since then he has remained in complete remission (see Fig. ). His prednisone was weaned over the following 6 months, and his prednisone was ceased. A repeat CTB and CTA showed resolution of the transverse sinus and posterior sagittal sinus thromboses and a decision was made to stop anti-coagulation.
The formula for computing Cockcroft-Gault is given by CrCl = ((140 - age) * adjusted weight * (gender_coefficient)) / (serum creatinine * 72), where the gender_coefficient is 1 if male, and 0.85 if female. The serum creatinine concentration is in mg/dL.
The patient's gender is male, which means that the gender coefficient is 1.
The patient is 23 years old. 
The concentration of creatinine is 75.0 µmol/L. We need to convert the concentration to mg/dL. Let's first convert the mass of creatinine from µmol to mg. The mass of creatinine is 75.0 µmol. To convert 75.0 µmol of creatinine to mol, multiply by the conversion factor 1e-06, giving us 75.0 µmol creatinine * 1e-06 mol/µmol = 7.5e-05 mol creatinine. To convert from mol creatinine to grams, multiply by the molar mass 113.12 g/mol, which will give 7.5e-05 mol creatinine * 113.12 g/mol = 0.008 g creatinine. To convert 0.008 g of creatinine to mg, multiply by the conversion factor 1000.0, giving us 0.008 g creatinine * 1000.0 mg/g = 8.0 mg creatinine. The current volume unit is L and the target volume unit is dL. The conversion factor is 10.0 dL for every unit of L. Our next step will be to divide the mass by the volume conversion factor of 10.0 to get the final concentration in terms of mg/dL. This will result to 8.0 mg creatinine/10.0 dL = 0.8 mg creatinine/dL. The concentration value of 75.0 µmol creatinine/L converts to 0.8 mg creatinine/dL. 
The formula for computing the patient's BMI is (weight)/(height * height), where weight is the patient's weight in kg and height is the patient's height in m.
The patient's height is 180.0 cm, which is 180.0 cm * 1 m / 100 cm = 1.8 m. The patient's weight is 93.0 kg. The patient's bmi is therefore 93.0 kg / (1.8 m * 1.8 m) = 28.704 kg/m^2.The patient's BMI is 28.7, indicating they are overweight/obese.
Because the patient is overweight/obese, we use the adjusted body weight formula to get the adjusted weight used for Cockroft-Gault Equation. Shown below is the computation for IBW (ideal body weight).
The patient's gender is Male.
The patient's height is 180.0 cm, which is 180.0 cm * 0.393701 in/cm = 70.866 in. 
For males, the ideal body weight (IBW) is calculated as follows:
IBW = 50 kg + 2.3 kg * (height (in inches) - 60)
Plugging in the values gives us 50 kg + 2.3 kg * (70.866 (in inches) - 60) = 74.992 kg.
Hence, the patient's IBW is 74.992 kg.Shown below is the computation for ABW (adjusted body weight).
To compute the ABW value, apply the following formula: ABW = IBW + 0.4 * (weight (in kg) - IBW (in kg)). ABW = 74.992 kg + 0.4 * (93.0 kg  - 74.992 kg) = 82.195 kg. The patient's adjusted body weight is 82.195 kg.

Using the Cockcroft-Gault equation:
CrCl = ((140 - age) * adjusted weight * gender_coefficient) / (serum creatinine * 72).
Plugging the patient's values gives us ((140 - 23) * 82.195 * 1) / (0.8 * 72) = 166.959 mL/min. Hence, the patient's creatinine clearance is 166.959 mL/min.