Diabetic glomerulosclerosis without diabetes mellitus--two case reports and a review of the literature.

The duration of diabetes mellitus and presence of hyperglycaemia appear to be important in the development of diabetic nephropathy. The presence of nodular glomerulosclerosis is thought to be pathognomonic of the condition. We report two patients with histological features of diabetic glomerulosclerosis who did not have diabetes mellitus. The discussion reviews the literature and concludes that diabetic glomerulosclerosis with normal glucose tolerance is very rare and that most cases are due to overt diabetes mellitus or a degree of glucose intolerance. However, cases with only minimal glucose intolerance suggest that factor(s) other than hyperglycaemia are responsible for diabetic renal damage.

Very late recurrence of renal vasculitis.

We report a case of renal vasculitis with a relapse occurring 9 and a half years after the original presentation. The plasma creatinine six months before relapse was only 118 mumol/l. During the initial illness there was histological evidence of glomerular damage but at the time of relapse renal biopsy showed the remaining glomeruli to be normal with the destructive process causing fibrinoid necrosis of arteries.

The late results of renal transplantation and the importance of chronic rejection as a cause of graft loss.

The results of 279 renal transplants performed in a single centre between 1974 and 1986 are reviewed. Improvements in the management of acute rejection and a reduction in mortality have resulted in an improvement in 1-year actuarial graft survival rates from 44% for transplants performed before 1980 to 68% for those performed after 1983. After the second year post-transplant there has been a steady rate of graft failure (6% per annum), mainly due to chronic rejection. In total 52 grafts have developed chronic rejection (19% of the total and 30% of those at risk at 6 months). Chronic rejection is assuming greater relative importance as a cause of graft loss as early results improve.

The nephrotic syndrome at presentation of insulin-dependent diabetes mellitus; cause or coincidence?

Two young women developed the nephrotic syndrome within 2 weeks of presenting with diabetes and starting insulin. One had a renal biopsy which showed changes consistent with 'minimal change nephrotic syndrome' on electron microscopy but no evidence of diabetic glomerulosclerosis. Neither patient received steroids; in one the oedema resolved spontaneously but the other required diuretics. This patient also had severe IgA-deficiency probably associated with epilepsy and/or phenytoin therapy and unrelated to the pathogenesis of the nephrotic syndrome. The nephrotic syndrome may rarely present coincidentally with, or soon after, insulin-dependent diabetes mellitus (IDDM). It must be distinguished from 'insulin oedema' and classical diabetic nephropathy which occurs later in the course of IDDM. All reported cases have either remitted spontaneously or responded to steroids.

Severely atypical changes in renal epithelium in biopsy and graft nephrectomy specimens in two cases of cadaver renal transplantation.

Severely atypical metaplastic and dysplastic changes were noted in the lining epithelium of collecting tubules and pelvis of the graft kidneys in two cases of cadaver renal transplants on immunosuppressive treatment with azathioprine and prednisolone. These changes were observed in case 1 in a needle biopsy and a nephrectomy specimen, 3 and 3.5 years after transplantation respectively. In a second case, the patient received two cadaver grafts, and both transplants showed similar changes 2 years after transplantation. The risk of malignant disease in kidney transplant recipients is now well recognized. The implications of the severe dysplastic changes noted in these two cases are discussed.

Basement membrane charge in human glomerular disease.

Fixed anionic charges in the mammalian glomerulus, on both the basement membrane and the epithelial cell foot processes, are believed to form an important part of the glomerular filtration barrier. There is good evidence that their loss causes proteinuria. The charges can be visualized ultrastructurally using cationic dyes, but the requirement of these techniques for perfusion or immersion of fresh tissue has largely confined such studies to experimental models. We have extended the widely used polyethyleneimine technique, to study the charge of glomerular basement membranes in human tissue reprocessed out of paraffin blocks up to 10 years old. We studied selected cases of glomerular disease, where the diagnosis was not in any doubt. In the majority of diseases studied, a continuous charge layer persisted despite severe abnormalities of the basement membrane. Two exceptions were found. In amyloidosis, accumulation of fibrils was associated with a considerable decrease or loss of stainable basement membrane charge. In S.L.E., numerous small defects in the charge layer were noted. The persistence of charge is contrary to reported findings in several animal models of glomerular disease, including puromycin nephrosis, Heymann nephritis and streptozotocin diabetes. Although this method is not subject to precise quantitative analysis, we conclude that in the majority of cases, proteinuria in man is not caused by an extensive loss of glomerular basement membrane anionic charge.

A comparison of fine needle aspiration cytology and tru-cut tissue biopsy in the diagnosis of acute renal allograft rejection.

Simultaneous Tru-cut biopsies and fine needle aspirations (FNAs) performed over a 2-year period on patients following renal transplantation were assessed by independent pathologists. When there was histological evidence of rejection, FNAs also demonstrated cellular features of rejection in 83% of cases, and this increased to 92% with repeated sampling. The presence of monocytes and histiocytes in FNAs correlated with vascular features of rejection on biopsy and failure to reverse the rejection process with steroids.

Widespread crystallisation of paraprotein in myelomatosis.

Two patients with myelomatosis leading to acute renal failure were found at autopsy to have extensive crystalline deposits of paraprotein within the capsular space of the glomeruli, renal tubules and renal blood vessels. In one case, crystalline deposits in the renal arteries had caused infarction of both kidneys. Both patients had extensive paraprotein deposits in the heart and in other tissues, leading to myocardial infarction in one case. This patient also had extensive pulmonary deposits of paraprotein without a local plasma cell infiltrate, an appearance which has not been described before. Crystalline deposition does not appear to be specifically associated with a single class of paraprotein. This type of disease, affecting many organs, may be more common than has generally been appreciated and should be considered as a cause of otherwise unexplained organ failure in patients with myelomatosis.

The future of histopathology--a personal view.

Pathology in general and histopathology in particular has recently spent some years in the doldrums associated with loss of purpose, direction, enthusiasm and credibility. The historical reasons for this and the reasons for recent emergence from this phase are to be used as a base for identifying needs for the future. As a result of technological advances and acceptance of some philosophical concepts, particularly that functional aspects need to be added to morphological studies, the view is expressed that histopathology should now be able to maintain its regained status as a foremost science in medical laboratory disciplines. These views were shared by Vincent McGovern in private conversation and demonstrated by him in his writings and practice. This written record by a friend is, in all humility and remembrance, dedicated to him.

Are patients with abnormal cervical smears adequately managed?

The outcome was assessed for all 1062 women in Nottingham who had a first report of abnormal cervical cytology in 1981. Satisfactory follow up could be found for only 628 (59%) of them. For 275 (26%) one subsequent normal smear had been reported but no further follow up requested. For 43 (4%), no subsequent test, after the abnormal smear, had been requested by the patient's general practitioner. Thirty patients (3%), 22 of whom had been tested at a special clinic, had not responded to a request for follow up. Even after extensive efforts we could not find the outcome in the remaining 86 (8%) of the patients. Adequate follow up of patients with abnormal cervical cytology is not being achieved. Improvements in the records systems and some changes in procedure should be made to reduce this problem.

Safety of treatment for subclinical osteomalacia in the elderly.

Forty one elderly patients admitted to hospital for acute illnesses were also found to have subclinical osteomalacia. Immediately before discharge, therefore, all were randomised to receive either vitamin D2 25 micrograms daily, alfacalcidol 0.5 micrograms daily, or placebo. Treatment was given for at least three months, those allocated to placebo then being switched to an active drug. Within the first three months of treatment with either of the active drugs most patients had exhibited a fall to normal in osteoid values. In only four treatment periods was there a mild increase in serum calcium concentration, and in no patient was this accompanied by deterioration in renal function. Any increase in serum creatinine concentration was invariably attributable to the underlying disease for which the patient had been admitted in the first place. Subclinical osteomalacia in the elderly may be corrected by relatively low doses of alfacalcidol (0.5 micrograms daily) or vitamin D2 (25 micrograms daily) given for three months. Such treatment is safe and not accompanied by a serious risk of hypercalcaemia or renal impairment.

Osteoid in bones of elderly patients without bone disease.

Bone samples were taken at post-mortem examination by Jamshidi needles from 88 elderly patients who were known to have normal bone biochemistry in life. The extent of osteoid in these samples is quantitatively described. In patients with normal creatinines the relative osteoid area ranges from 0 to 3.7% and trabecular osteoid surface percentage ranges from 0 to 23%, but higher values were seen in those with raised creatinines. Osteoid extent did not vary with age, sex or time of year. Descriptions of other series of control bone biopsies in the literature are reviewed and it is suggested that relative osteoid area greater than 3.5% or osteoid surfaces greater than 25% should be considered excess osteoid.

Screening for subclinical osteomalacia in the elderly: normal ranges or pragmatism?

Although osteomalacia is known to be common in some sections of the elderly population, the disease is often subclinical and there is uncertainty about the point at which treatment is necessary. Identification and treatment of osteomalacia are inseparably bound; the response of varying degrees of subclinical disease to treatment with vitamin D or alfacalcidol is described here. The response is assessed in relation to a simply derived reference range based on standard biochemical measurements together with a Jamshidi needle biopsy of the iliac crest. Although this technique does not define a truly normal range it identifies a treatable abnormality which could form the basis of further study of the problem of subclinical osteomalacia in the elderly.

Endoscopic review of patients who have had gastric surgery.

Seventy one patients who had had operations on their stomachs over 15 years previously were examined by endoscopy and multiple mucosal biopsy sampling. Sixty six had histologically proved gastritis (56 chronic atrophic gastritis, 10 superficial gastritis), 38 intestinal metaplasia, and 11 epithelial dysplasia. In three cases the epithelial dysplasia was severe (carcinoma in situ). One patient had an infiltrating carcinoma and another, whose biopsy appearances were reported as severe dysplasia, developed a carcinoma of the stomach eight months later. All patients having undergone gastric surgery more than five years previously should be screened endoscopically and any found to have moderate dysplasia subjected to regular endoscopic screening thereafter. Patients with severe dysplasia (carcinoma in situ) should be considered for radical surgery.