Clinical and Morphological Aspects of the Managment of Crescentic Anti-glomerular Basement Membrane Antibody (Anti-GBM) Nephritis/Goodpasture's Syndrome

Twenty-two patients with crescentic anti-GBM nephritis or Goodpasture'ssyndrome with renal impairment were reviewed. All patients weretreated with a combination of plasma exchange and immunosuppression. Sixteen patients (73 per cent) showed improvement in renal function(> 30 per cent reduction in serum creatinine level) apparentlyin response to treatment, and nine patients (41 per cent) madelong-term recoveries in renal function. The most important features carrying a bad prognosis were totalanuria, and/or a very high percentage of glomeruli showing crescents(> 85 per cent) in the initial renal biopsy. Some patientswith other so-called ‘bad’ prognostic features,including severely impaired renal function at presentation,oliguria and the need to institute dialysis had unexpected markedimprovement in renal function and/or recovered renal functionin the long term provided treatment with plasma exchange wasbegun promptly and maintained for a sufficient period to allowresolution of the disease process. Renal biopsies at the beginning and later proved to be an extremelyvaluable guide to the progress and outcome of the disease.     

Gastrointestinal manifestations of systemic vasculitis

Systemic vasculitis is known to affect the gastrointestinal tract but the nature of the complication is poorly characterized. Out of 65 patients with systemic vasculitis, the majority of whom had renal disease, the intestine was found to be affected in 18. These comprised four of eight patients with polyarteritis nodosa, nine of seventeen with microscopic polyarteritis, four of thirty-six with Wegener's granulomatosis and one of four with Churg-Strauss syndrome. The features included abdominal pain (85 per cent), diarrhoea (50 per cent), gut haemorrhage (44 per cent) and abnormal liver function tests (50 per cent). Manifestations of gastrointestinal disease were evident at presentation in half the patients and led to a fetal outcome in five. Ileus, mucosal abnormalities, perforation and slow transit were evident radiographically, and selective visceral angiography showed aneurysms or organ infarcts in five patients. Histological assessment of gut biopsies (chiefly rectal) revealed non-specific inflammation or ulceration in nine patients and intramucosal haemorrhage in two. Focal areas of necrosis and ulceration in colonoscopic biopsies were highly suggestive of vasculitis whereas arteritis was only found in one full thickness biopsy. Hence the diagnosis of gastrointestinal complications depends largely on clinical evidence. In patients who survived, the gastrointestinal features remitted as the systemic illness improved following treatment with steroids, cyclophosphamide or plasma exchange.     

Infection and Immunosuppression: A STUDY OF THE INFECTIVE COMPLICATIONS OF 75 PATIENTS WITH IMMUNOLOGICALLY-MEDIATED DISEASE

We have studied the infective complications in a group of 75patients with immunologically-mediated disease who requiredhigh dose immunosuppression. There were 22 patients with anti-glomerularbasement membrane antibody disease, 19 patients with systemiclupus erythematosus, 18 with Wegener's granulomatosis and 16patients with other forms of systemic vasculitis. The infection rate was 3.69 infections/patient, or 0.74 infections/patient/weekof immunosuppression. Bacteria were the commonest infectingorganisms (76.1 per cent); serious opportunist viral and fungalinfections were less frequent (10.7 per cent) but opportunistpneumonias were an important cause of death. Sixteen patientsdied (21 per cent) and in 10 of these (62.5 per cent) deathwas considered to be primarily due to infection. Analysis of six aspects of host susceptibility to infection(age, renal function, dose of prednisolone, cyclophosphamideand azathioprine, and number of plasma exchanges) revealed nosingle factor as predisposing to infection in the whole group,but in 23 patients who suffered severe infective complications,renal impairment and increasing doses of prednisolone were associatedsignificantly, particularly in combination (p = 0.06). Cyclophosphamidewas associated with infection only in the presence of neutropenia,which was rare (13 infections in nine patients). The durationof plasma exchange was not related to the frequency of infection. Fifty patients needed an arteriovenous shunt to provide vascularaccess for haemodialysis or plasma exchange, and septicaemiaoccurred in 13; only two episodes of septicaemia were seen inpatients without a shunt.     

Gastrointestinal Manifestations of Systemic Vasculitis

Systemic vasculitis is known to affect the gastrointestinaltract but the nature of the complication is poorly characterized.Out of 65 patients with systemic vasculitis, the majority ofwhom had renal disease, the intestine was found to be affectedin 18. These comprised four of eight patients with polyarteritisnodosa, nine of seventeen with microscopic polyarteritis, fourof thirty-six with Wegener's granulomatosis and one of fourwith Churg-Strauss syndrome. The features included abdominalpain (85 per cent), diarrhoea (50 per cent), gut haemorrhage(44 per cent) and abnormal liver function tests (50 per cent).Manifestations of gastrointestinal disease were evident at presentationin half the patients and led to a fatal outcome in five. Ileus,mucosal abnormalities, perforation and slow transit were evidentradiographically, and selective visceral anglography showedaneurysms or organ infarcts in five patients. Histological assessmentof gut biopsies (chiefly rectal) revealed non-specific inflammationor ulceration in nine patients and intramucosal haemorrhagein two. Focal areas of necrosis and ulceration in colonoscopicbiopsies were highly suggestive of vasculitis whereas arteritiswas only found in one full thickness biopsy. Hence the diagnosisof gastrointestinal complications depends largely on clinicalevidence. In patients who survived, the gastrointestinal featuresremitted as the systemic illness improved following treatmentwith steroids, cyclophosphamide or plasma exchange.     

Renal failure in the elderly

A pilot study recording the incidence, management and outcome of renal failure in elderly patients presenting to three geriatric units in a six-month period is described. A total of 4001 patients were admitted during this time and 273 patients were considered to have renal failure at presentation (criteria, plasma urea level greater than or equal to 17 mmol/l and/or creatinine level greater than or equal to 160 mumol/l). In 151 patients (55 per cent) the cause was pre-renal and this form of renal failure had a good prognosis; over 60 per cent recovered and increasing age did not affect prognosis adversely. Ninety-six patients (35 per cent) had intrinsic renal disease which was commoner in younger patients and had a mortality rate of 48 per cent. In the majority of patients renal failure was mild, only 24 per cent having a urea level greater than 31 mmol/land/or creatinine level greater than 400 mumol/l.     

Improvement of Renal Function During Long-term Treatment of Severe Hypertension with Minoxidil

Sixty-nine patients with refractory hypertension were treatedwith minoxidil and in 66 good control of blood pressure wasachieved. Renal function was stabilized in 31 patients in whomthe serum creatinine was normal at presentation. Twenty-eightpatients with impaired renal function had a substantial fallin serum creatinine (25 per cent) during the first three tosix months of treatment and this improvement was maintained.In contrast, renal function in six out of seven patients withprimary renal disease continued to deteriorate despite adequatecontrol of blood pressure. Effective control of blood pressure prevents or reverses impairmentof renal function in patients with refractory hypertension notassociated with primary renal disease.     

Improvement of renal function during long-term treatment of severe hypertension with minoxidil

Sixty-nine patients with refractory hypertension were treated with minoxidil and in 66 good control of blood pressure was achieved. Renal function was stabilized in 31 patients in whom the serum creatinine was normal at presentation. Twenty-eight patients with impaired renal function had a substantial fall in serum creatinine (25 per cent) during the first three to six months of treatment and this improvement was maintained. In contrast, renal function in six out of seven patients with primary renal disease continued to deteriorate despite adequate control of blood pressure. Effective control of blood pressure prevents or reverses impairment of renal function in patients with refractory hypertension not associated with primary renal disease.     

Plasma exchange treatment and prognosis of Guillain-Barré syndrome.

A retrospective analysis of case notes was undertaken for 52 patients presenting to Guy's Hospital with Guillain-Barré syndrome between August 1987 and September 1990. Twelve months after onset 61 per cent of patients had recovered completely, 35 per cent were still significantly disabled and two patients (4 per cent) had died. Forty-eight of the patients (92 per cent) were treated with plasma exchange. The frequency of morbidity related to this treatment was low, and plasma exchange was not responsible for either of the deaths. Outcome for all patients treated with plasma exchange between January 1985 and September 1990 was compared with that of 64 patients with Guillain-Barré syndrome seen in 1983 and 1984 who were not treated in this way. Time to walking unaided was significantly better (median 58 days compared with 86 days, p = 0.031), as was the median duration of ventilation (16.5 compared with 36 days, p = 0.004). Factors which had been found to predict an adverse outcome in previous studies (requirement for ventilation, age over 40 years, time to becoming bedbound less than 4 days, and small distally evoked abductor pollicis brevis muscle action potential) were not significantly associated with a poor prognosis in this study. The features associated with persisting disability were time to improvement more than 21 days, preceding diarrhoea and older age.     

The clinical spectrum of acute glomerulonephritis and lung haemorrhage (Goodpasture's syndrome)

The aetiology, clinical features and outcome of 40 patients presenting with Goodpasture's syndrome (glomerulonephritis with haemoptysis and pulmonary infiltrates) are reviewed. The diseases of the patients studied could be divided into three groups: antiglomerular basement membrane (anti-GBM) antibody-induced disease (7/40); systemic vasculitis (22/40) and idiopathic Goodpasture's syndrome (i.e. no systemic disease or anti-GBM antibody detected) (11/40). Overall mortality was 57.5 per cent (anti-GBM disease 4/7; systemic vasculitis 15/22; and idiopathic Goodpasture's syndrome 4/11). Most patients died of disease progression or infection. End-stage renal failure developed in 26 patients (anti-GBM (7), vasculitis (14) and idiopathic Goodpasture's syndrome (5). End-stage renal failure developed in 23 of 24 patients presenting with a creatinine of greater than 600 microM/l regardless of the aetiology of Goodpasture's syndrome or treatment used. Review of renal histology showed that all had proliferative nephritis, with 80 per cent of patients having more than 30 per cent crescents. Thus Goodpasture's syndrome was associated with a wide variety of underlying disease. It had a poor prognosis, with the degree of renal impairment at presentation, the extent of crescent formation and the nature of the underlying disease being the major determinants of outcome.     

Renal biopsy in patients with unexplained renal impairment and normal kidney size

We report renal biopsy findings in 109 patients with unexplained renal impairment (serum creatinine greater than 0.15 mmol/l) and normal-sized non-obstructed kidneys. The most common histological lesions were interstitial nephritis, rapidly progressive glomerulonephritis and a variety of other types of glomerulonephritis. The groups could not be distinguished by the presence or absence of hypertension, haematuria, proteinuria, or features of systemic disease. However interstitial nephritis was found more frequently in patients presenting with one or none of these features and rapidly progressive glomerulonephritis in patients presenting with three or more. All four patients with none of these features had interstitial lesions. Fifty-two per cent of patients with interstitial nephritis improved and 60 per cent of the patients with rapidly progressive glomerulonephritis who received immunosuppressive treatment improved or remained stable with treatment. The benefits of a biopsy diagnosis were almost wholly confined to these two groups. Complications were recorded in nine patients - prolonged macroscopic haematuria in six and symptomatic perirenal haematomata in three. Six required blood transfusion. One required nephrectomy to control haemorrhage and subsequently died. Percutaneous renal biopsy is not without risk in patients with renal impairment but the benefits of diagnosing interstitial nephritis and rapidly progressive glomerulonephritis outweigh the disadvantages.     

Systemic lupus erythematosus with membranous lupus nephropathy in Malaysian patients

Thirty-one patients with systemic lupus erythematosus had membranous lupus nephropathy (MLN). They were divided into two groups. Group I consisted of 13 patients who had pure MLN but the patients in Group 2 had segmental proliferation in up to 35 per cent of their glomeruli. The rest of the glomeruli had purely membranous change. The patients of Group 2 were no different from the other MLN patients in terms of age, sex and race. The extrarenal disease in both groups was extensive and severe. The renal disease was usually associated with the nephrotic syndrome or oedema but was asymptomatic throughout in one patient. Both renal and extrarenal features responded to treatment initially but relapses were frequent and often severe. Relapses often occurred as treatment was discontinued or medication reduced. Survival at six years in Group I was 62 per cent and in Group 2 was 50 per cent. Only one patient died with renal failure although five patients had impaired renal function at death. The chief causes of death were disease of the central nervous system and infection.     

Persistent infection as a cause of renal disease in patients submitted to renal biopsy: a report from the Glomerulonephritis Registry of the United Kingdom MRC

We report the results of a survey within the United Kingdom of the importance of persistent systemic infection in patients with unexplained renal disease who undergo renal biopsy. Twenty-two units participated. Overall 1.7 per cent of patients undergoing biopsy had an infection but there was large variation between units. Interstitial nephritis and amyloid deposits were more common in patients with infection, and minimal change nephropathy was less common than in patients undergoing biopsy but without infection. The respiratory tract was the most common site of infection but was rarely associated with glomerulonephritis of which the most common cause was infective endocarditis. Drug treatment may have caused the renal lesion in 16 per cent of patients. Amyloid deposits, present in 13.6 per cent of patients, was the most common cause of progressive renal failure. Most other patients had some improvement in renal function once the putative cause, whether infection or antibiotic, was removed.     

Systemic Lupus Erythematosus with Membranous Lupus Nephropathy in Malaysian Patients

Thirty-one patients with systemic lupus erythematosus had membranouslupus nephropathy (MLN). They were divided into two groups.Group 1 consisted of 13 patients who had pure MLN but the patientsin Group 2 had segmenta! proliferation in up to 35 per centof their glomeruli. The rest of the glomeruli had purely membranouschange. The patients of Group 2 were no different from the otherMLN patients in terms of age, sex and race. The extrarenal disease in both groups was extensive and severe.The renal disease was usually associated with the nephroticsyndrome or oedema but was asymptomatic throughout in one patient.Both renal and extrarenal features responded to treatment initiallybut relapses were frequent and often severe. Relapses oftenoccurred as treatment was discontinued or medication reduced. Survival at six years in Group 1 was 62 per cent and in Group2 was 50 per cent. Only one patient died with renal failurealthough five patients had impaired renal function at death.The chief causes of death were disease of the central nervoussystem and infection.     

Percutaneous transluminal angioplasty improves blood pressure and renal function in renovascular hypertension

Thirty-three patients with renal angiographic evidence of significant renal artery stenosis were referred for percutaneous transluminal angioplasty. The indications were poorly controlled hypertension (n = 13) or hypertension associated with deteriorating renal function (n = 20). Their mean age was 56 (23-73) years (12 males, 21 females). Causes of the renal artery stenosis were fibromuscular dysplasia (n = 8) and atheromatous changes (n = 25). Four patients were excluded, three due to technical failure. Forty-five angioplasties were performed in 29 patients with a mean observation period after angioplasty of 18 (one to 60) months. During this period eight patients (28 per cent) had a diastolic blood pressure of less than 90 mmHg without antihypertensive drugs, a further 15 patients (52 per cent) had improved blood pressure control with a significant reduction in the number and amount of antihypertensive drugs, but six patients (20 per cent) showed no improvement in blood pressure. Hypertension associated with the stenosis of fibromuscular dysplasia responded better to angioplasty than hypertension associated with atheromatous renal artery stenosis. Improvement in renal function was noted in eight patients with no change in 16 patients. Two patients with end-stage renal failure and atheromatous intrarenal vascular disease became dialysis dependent within four weeks of the procedure. One major and four minor complications occurred but there were no deaths related to angioplasty. Together with results from other centres this study indicates that percutaneous transluminal angioplasty should be considered the initial treatment choice for all patients with renovascular hypertension due to fibromuscular dysplasia and atheromatous renal artery stenosis.     

Renovascular hypertension: ten years' experience in a regional centre

In a unit serving a population of three million, 60 hypertensive patients with renovascular disease were identified over a 10-year period. The presence of renovascular disease was usually suggested by intravenous urography (IVU), although this was falsely negative in 21 per cent of cases; isotope renography (IR) was normal in a similar proportion of patients (25 per cent). Eight patients were treated medically and 52 underwent surgical procedures; nephrectomy in 32, autotransplantation in 10, by pass graft in six and percutaneous transluminal angioplasty in four. Twenty-three per cent of patients were cured, 37 per cent improved and 40 per cent unchanged one year after surgery, but the response could not be accurately predicted. Clinical features were of some value in that those patients most likely to benefit from surgery were younger, had less severe hypertension of shorter duration, smoked less, had less severe retinopathy and less cardiomegaly. There was also a trend for those with better renal function and less electrocardiographic evidence of left ventricular hypertrophy to benefit from surgery. The IVU and IR did not predict response to surgery but arteriographic appearances of fibromuscular dysplasia indicated there should be a favourable response. The renal vein renin ratio, basal or stimulated, was of no prognostic value since approximately two-thirds of patients with ratios above or below the threshold value had some benefit from surgery. We conclude that the surgical treatment of renovascular hypertension is worthwhile but the number of patients suitable for surgery is small. Clinical features and the results of simple investigations provided the best guide to surgical outcome in our patients.     

Ventricular function in patients with silent myocardial ischemia before and following aortocoronary bypass operation

In 12 patients with silent myocardial ischemia (fall of the ejection fraction (EF) greater than or equal to 5%, without angina pectoris) and in 15 symptomatic patients with coronary heart disease (fall of the EF during exercise EF greater than or equal to 5%, with angina pectoris), the left ventricular ejection fraction and the diastolic function (Peak Filling Rate, PFR; Time to Peak Filling Rate, TPFR) were evaluated before coronary artery bypass surgery and afterwards by the aid of the Nuclear Stethoscope. Our results showed a slight insignificant improvement in the EF from 60 +/- 8.3 per cent at rest to 66 +/- 7.9 per cent vs. 57 +/- 12 per cent to 62.6 +/- 9 per cent in patients with silent ischemia and in patients with angina pectoris after surgery. In contrast to this the EF increased significantly during exercise both in patients with silent ischemia from 52.0 +/- 15.2 per cent to 70.1 +/- 7.9 per cent and in symptomatic patients after revascularisation from, 49 +/- 11.7 per cent on to 64.2 +/- 8.4 per cent (both p less than 0.0001). There was also a similar significant improvement in the diastolic function, whereby the PFR was enhanced from 2.52 +/- 0.54 EDV/sec to 3.31 +/- 0.87 EDV/sec (p less than 0.02) in patients with silent myocardial ischemia and from 2.55 +/- 0.86 EDV/sec to 3.40 +/- 0.98 EDV/sec (p less than 0.02) in symptomatic patients. The TPFR showed a similar improvement.     

Renal Failure in the Elderly

A pilot study recording the incidence, management and outcomeof renal failure in elderly patients presenting to three geriatricunits in a six-month period is described. A total of 4001 patientswere admitted during this time and 273 patients were consideredto have renal failure at presentation (criteria, plasma urealevel 17 µmol/1 and/or creatinine level 160. In 151patients (55 per cent) the cause was pre-renal and this formof renal failure had a good prognosis; over 60 per cent recoveredand increasing age did not affect prognosis adversely. Ninety-sixpatients (35 per cent) had intrinsic renal disease which wascommoner in younger patients and had a mortality rate of 48per cent. In the majority of patients renal failure was mild,only 24 per cent having a urea level greater than 31 µmol/1and/orcreatinine level greater than 400µmol/l.     

Renal disease associated with circulating antineutrophil cytoplasm activity.

We report our detailed observations on a group of 30 consecutive patients with renal disease, histologically demonstrated glomerulitis or necrotizing vasculitis, and circulating antineutrophil cytoplasm activity (ANCA). The annual incidence of ANCA-related renal disease was seven cases per million population. The sensitivity of serum ANCA for histologically proved glomerular vasculitis was 79 per cent, with a specificity of 87 per cent. Most patients responded to treatment with cyclophosphamide and steroids but complications of therapy occurred in just over half the patients and were serious in 20 per cent. Actuarial survival at 1 year was 60 per cent. Age and dialysis requirement did not influence outcome and the only identified adverse prognostic factor was hypoxic lung disease. We conclude that the association of ANCA with renal disease is not rare and that positive serology accurately identifies a homogeneous group of patients with similar clinical, histological, and prognostic features. Separation of these patients into those with the disease entities of Wegener's granulomatosis and microscopic polyarteritis is not straightforward on clinical and histological criteria, and such a distinction does not yield useful therapeutic or prognostic information. Simple urinalysis should always be carried out in patients with undiagnosed systemic illness in order to identify renal disease. ANCA-related renal disease can be treated successfully with cyclophosphamide and steroids and elderly patients should not be excluded from treatment, including dialysis if necessary. The ANCA test is simple and quick to perform and, in the appropriate clinical setting, accurately identifies patients who may benefit from immunosuppressive treatment before a histological diagnosis can be established.     

Clinicopathological Features of Childhood Nephrotic Syndrome in Northern Nigeria

The clinicopathological features of childhood nephrotic syndromein northern Nigeria were studied in 100 consecutive patients.The patients presented with gross anasarca and very low serumalbumin, which was <15 g/1 in 30 patients. The three mostfrequent histological diagnoses in 98 renal biopsies were membranoproliferativeglomerulonephritis (25), quartan malarial nephropathy (20),and proliferative glomerulonephritis (19): together they accountedfor 65 per cent of all biopsies. Only nine patients had minimalchange nephropathy. Antigens were detected by immunofluorescencein the glomeruli of 70 of 76 biopsies (92 per cent): Plasmodiummalariae was detected in 25 per cent and hepatitis B surfaceantigen in 24 per cent. The disease was characterized by progressivedeterioration in renal function and a high mortality rate of13 per cent. Nine of the 13 deaths occurred within one yearof diagnosis.     

Efficacy of plasma exchange in severe idiopathic rapidly progressive glomerulonephritis. A report of ten cases

The vast majority of patients with idiopathic rapidly progressive glomerulonephritis (RPGN) develop irreversible renal failure within weeks to months. We report a retrospective study of 10 patients with idiopathic RPGN who were treated with plasma exchange in addition to steroids and immunosuppression. Renal biopsies were obtained in nine patients. RPGN without immune complexes was present in four, immune complex disease in four, and anti-glomerular basement membrane disease in two. Renal function did not recover in those patients with anti-glomerular basement membrane disease. In contrast, seven of eight patients without auto-antibodies to basement membranes responded to therapy, and four did not need dialysis for two years or more. The sustained improvement in renal function in these seven patients suggests the need for evaluation of plasma exchange as an adjunct to steroids and immunosuppression in a prospective, controlled study in RPGN.