R. P. Burden

Analysis of Reciprocal Creatinine Plots by Two-Phase Linear Regression

The progression of renal diseases is often monitored by the serial measurement of plasma creatinine. The slope of the linear relation that is frequently found between the reciprocal of creatinine concentration and time delineates the rate of change in renal function. Minor changes in slope, perhaps indicating response to therapeutic intervention, can be difficult to identify and yet be of clinical importance. We describe the application of two-phase linear regression to identify and characterise changes in slope using a microcomputer. The method fits two intersecting lines to the data by computing a least-squares estimate of the position of the slope change and its 95% confidence limits. This avoids the potential bias of fixing the change at a preconceived time corresponding with an alteration in treatment. The program then evaluates the statistical and clinical significance of the slope change and produces a graphical output to aid interpretation.

Renal Cell Carcinoma Presenting as Nephrotic Syndrome

A 64-year-old woman presenting with a history of increasing oedema was found to have nephrotic syndrome with a 24-hour urinary protein excretion of 20.7 g and renal impairment with an initial serum creatinine level of 197 mumol/l (2.16 mg/dl). A renal tumour was demonstrated by ultrasound scanning and subsequent nephrectomy revealed a renal carcinoma extending as far as the resected end of the renal vein. Histology of the kidney not involved by the tumour showed normal light microscopic appearances, with electron microscopy demonstrating foot process fusion, suggesting a diagnosis of minimal-change nephropathy. Nephrotic syndrome is a rare complication of renal cell carcinomas, and it is particularly uncommon for minimal change nephropathy to be associated with solid tumours.

Association of IgA Nephropathy and Myasthenia gravis

Dr. Andrew Innes, Nottingham Health Authority, City Hospital, Hucknall Road, Nottingham NG5 1PB (UK) Dear Sir, We were interested to read the recent article in Neph-ron by Miyazaki et al. [1] which described 3 patients in whom IgA nephropathy was associated with myasthenia gravis. In all 3 cases, myasthenia gravis appeared after the discovery of glomerulonephritis. We have also noted a patient with both of these conditions in whom myasthenia gravis and a subsequent total thymectomy preceded the IgA nephropathy. A 25-year-old male presented with ocular myasthenia gravis in 1981 and was initially treated with steroids and azathioprine. There was a poor response to this regime and shortly thereafter a total thymectomy was performed with a good initial result. No thymoma was demonstrated. In 1986, he was first noted to have microscopic haematuria and hypertension and at that time was on oral steroids for an exacerbation of this myasthenic symptoms. He presented to a medical ward 1 year later with a vasculitic skin rash affecting his feet, calves, hands and forearms. He continued to have microscopic haematuria and remained hypertensive (blood pressure 170/130). He never noted macroscopic haematuria. Investigation results were as follows: plasma creatinine 84 μmôl/l, urinary protein 0.26 g/24 h, intravenous urogram normal; C3, C4 and C3d were all within the normal range. Autoantibodies were negative, serum IgG and IgM levels were normal but serum IgA level was mildly elevated at 4.54 g/l (normal range 1.25–4.25 g/l). Renal biopsy yielded twenty-six glomeruli of which two were globally sclerosed. The remainder were normal on light microscopy but electron microscopy and immunoperoxidase studies demonstrated large mesangial IgA deposits with smaller amounts of C3 in a similar distribution and in small blood vessels. A punch biopsy of skin included a purpuric macule 0.4 cm in diameter. This biopsy showed severe acute neutrophilic vasculitis largely confined to upper dermal vessels. In the mid-dermis a larger muscular artery demonstrated neutrophilic vasculitis and fibrinoid necrosis of the walls. The skin rash slowly subsided spontaneously but the patient continues to require antihypertensive medication. The most recent plasma creatinine was 93 μmol/l. This individual was thought to have both IgA nephropathy and a vasculitis of the skin. It is also possible that the skin rash and renal lesion are both manifestations of Henoch-Schönlein purpura. Although the skin changes are in keeping with this diagnosis, the renal lesions show no evidence of vascular disease and are characteristic of IgA nephropathy. IgG and IgM are absent and there are no basement membrane deposits such as would be expected in Henoch-Schönlein purpura. As the microscopic haematuria was identified 1 year before the clinical manifestations of skin vasculitis this would seem to be a separate unrelated