Membranous Nephropathy: LONG-TERM FOLLOW-UP AND ASSOCIATION WITH NEOPLASIA

Sixty-six patients of all ages whose renal biopsy appearancessatisfied strict criteria for the histopathological diagnosisof membranous nephropathy were studied and followed for a meanof 5-4 years (range 1 to 20 years). From initial investigationseven patients were found to have associated neoplasia, andin two patients the condition followed treatment with a mercurialdiuretic and gold. One patient was Australia antigen positive.Two patients developed renal vein thrombosis, but in both thisappeared to follow not precede their nephrotic syndrome. Inthe remaining 56 patients there was no associated factor. During the follow-up period, approximately one-quarter of thepatients (15) died, nine from renal failure; one-quarter (10)had a persistent nephrotic syndrome, another one-quarter (15)proteinuria of lesser degree. The final one-quarter (16) arenow in complete remission. The prognosis of the 54 patientswith an initial nephrotic syndrome was poorer than the 12 withlesser proteinuria and no oedema at onset; five of 11 childrenwere in complete remission when last seen. All but one of thenine patients who developed terminal chronic renal failure 4to 18 years from onset had an unremitting nephrotic syndrome,and eight of the 10 currently alive with a persistent nephroticsyndrome have reduced renal function. Renal functional deteriorationdid not occur in the absence of proteinuria. There was only slight correspondence between the stage of biopsyappearance, glomerular filtration rate at time of biopsy, timeof the biopsy from apparent onset, or status at last follow-up.Staging is therefore of limited prognostic value. Twenty-twopatients were treated with corticosteroids for 2 to 36 months;we detected no short or long-term benefit when compared to patientsnot so treated. ¹Present address: Princess Alexandra Hospital, Ipswich Road,Woolloongabba, Brisbane, Queensland, Australia.     

Intrarenal Vascular Changes in Adult Patients with Recurrent Haematuria and Loin Pain--A Clinical, Histological and Angiographic Study

Clinical features have been correlated with renal function,histology and selective renal angiography in 19 patients withrecurrent painless haematuria, recurrent loin pain, or bothhaematuria and loin pain in whom urinary infection, calculiand anatomical abnormalities of the urinary tract had been excluded.No deterioration in renal function was observed in any patientover periods of up to nine years. Although all patients showedsimilar glomerular changes histologically, consisting of focaland segmental mesangial thickening and proliferation and periglomerularfibrosis, mild tubular damage was more common in those withloin pain. All patients with loin pain whether or not they hadhaematuria, had abnormal renal angiograms consisting of focalor generalized vascular lesions sometimes associated with corticalinfarcts. The possible aetiological factors are discussed withparticular reference to oestrogen-containing compounds. ¹Present address: Wessex Regional Renal Unit, St. Mary's GeneralHospital, Portsmouth. ²Present address: Renal Unit, Walsgrave Hospital, Coventry.     

Progression and Remission in the Nephrotic Syndrome Associated with Quartan Malaria in Uganda

The clinical history of the nephrotic syndrome associated withquartan malaria in Uganda has been defined by analysis of agroup of 115 patients. This group was derived from 156 patientswho presented with the nephrotic syndrome by the exclusion ofall patients in whom there were reasons to suspect that theaetiology was other than malarial. Despite a common immunopathologicalmechanism the clinical history varied. The prognosis was foundto be related to the appearance of the initial biopsy. The over-allmortality was 24 per cent, 26 per cent remained in protein-freeremission when last seen, and the remainder had persistent proteinuria.The potential for remission was related to the severity of theglomerular changes seen in the initial biopsy and remissiononly occurred in patients whose initial biopsy showed mild proliferativechanges. Full remission with loss of proteinuria was associatedwith the disappearance of protein deposits demonstrable by immunofluorescence, and occurred without substantial alteration inthe glomerular changes on light microscopy. Progression to renalfailure and death was only seen in those patients whose initialbiopsy showed marked glomerular proliferation or membrano proliferativechanges. Partial remission to light proteinuria whether it occurredspontaneously or following treatment conferred a definite improvementin the prog nosis. Assessment of the value of treatment withimmuno-suppressive drugs and other agents both of this disease,and also, possibly, of other types of glomerulo nephritis causedby soluble complexes, must take into account the value of apartial remission and the limited potential for healing in thosepatients with marked glomerular changes. ¹ Present address: St. Thomas's Hospital, London, S.E. 1.     

Causes of Recurrent Haematuria

Eighty-two patients with recurrent haematuria were investigatedand divided into five groups according to clinical and histologicalfindings. In patients with no documented history of acute nephritis,approximately equal numbers had normal renal histology, focalnephritis, and diffuse proliferative glomerulonephritis. Patientswith diffuse proliferative glomerulonephritis showed a femalepreponderance, had a higher incidence of frank haematuria, raisedsedimentation rate, and raised antistreptolysin O titre. Unlikeprevious reports, two of 26 patients with focal nephritis showeddeterioration of renal function on follow up, whilst C'3 levelswere diminished in three patients. Hypertension was observedin 10 per cent of patients with optically normal renal histologyor focal nephritis. The significance of these results are assessedin relation to those reported in the literature. ¹Senior Registrar in Clinical Medicine. ²Lecturer in Clinical Medicine. ³Senior Pathologist. ⁴Professor of Clinical Medicine.     

Behcet's Syndrome with Obstruction of the Venae Cavae: A REPORT OF SEVEN CASES

Seven patients with Behçet's syndrome are presented.All fulfilled at least two of the three major criteria of thesyndrome—oral ulceration, genital ulceration, and ocularmanifestations. In addition, in all the patients either thesuperior vena cava (five cases) or the inferior vena cava (fivecases) or both (three cases) were partially or totally occludedas demonstrated by angiography. Analysis of these cases, togetherwith 10 cases reported in the literature, indicates that inBehçet's syndrome the caval thrombosis begins in theseor adjacent large veins themselves and the initiating eventis probably vasculitis. It is concluded that the eaval thrombosisis not a mere association, but an integral manifestation ofBehçet's syndrome. ¹Present address: Dept. of Medicine, Jersey City Medical Center,Jersey City, N.J., U.S.A. ²Present address: The Moore Clinic, Johns Hopkins Hospital,Baltimore, Md., 21205, U.S.A. (Reprints from F. L. Özer). ³Present address: Dept. of Medicine, University of KentuckySchool of Medicine, Louisville, Ky., U.S.A.     

Acute Reversible Renal Failure in Patients with Acute Cholecystitis and Cholangitis

Although acute renal failure is a well recognized complicationof several extra-hepatic biliary tract diseases especially biliarytract surgery in the presence of obstructive jaundice, thereis little information concerning renal failure in acute cholecystitis.Renal function was assessed in 14 patients with acute cholecystitisand two with acute cholangitis. Six patients had no evidenceof renal impairment, four had modest elevations of plasma ureaand creatinine concentrations and six had acute reversible renalfailure of whom three required peritoneal dialysis. Only onepatient was hypovolaemic and in the remainder there was evidencethat intravascular coagulation was responsible for the renalfailure. It is suggested that bacteraemia was the initiatingfactor. The therapeutic implications of these findings are discussed. ^*Present address: Wessex Regional Renal Unit, St. Mary's GeneralHospital, Portsmouth     

Mechanism of antinephritic effect of proteinase inhibitors in experimental anti-GBM glomerulopathy

We have previously documented amelioration of rat autologous anti-GBM nephritis with the antiproteolytic drugs l-aminocaproic acid (EACA) and aprotinin, given from the day of induction or later in the course of disease. In the present study we investigated potential mechanisms of this effect by assessing interactions of the drugs with proteinase-dependent generation of superoxide anion in glomeruli, and their influence on both GBM degradation in vitro and activity of glomerular proteolytic enzymes. Release of O₂^- by enzymatically disrupted glomeruli, isolated from nephritic control or EACA/aprotinin-treated rats, was measured with the ferricytochrome reduction method and its activity was correlated with proteinuria and glomerular cellularity at the early phase of the disease. The hydroxyproline release assay was used to quantitate degradation of rat GBM in vitro by leukocyte proteinases stimulated by phorbol myristate acetate (PMA), in the presence or absence of EACA and aprotinin. Finally, the activities of elastase, cathepsins B and L, and plasmin, together with collagenase-like activity, were assessed fluorimetrically in homogenates of glomeruli isolated from control and antiproteolytic-drug-treated nephritic rats. EACA and aprotinin notably inhibited production of superoxide by nephritic glomeruli (by 47% and 66%, respectively), and this effect was not significantly correlated with proteinuria or glomerular hypercellularity at the early stage of disease. On the other hand, generation of O₂^- by glomeruli of untreated nephritic rats was notably correlated with total glomerular cell counts and numbers of macrophages infiltrating glomeruli. PMA-stimulated neutrophils and macrophages caused degradation of isolated rat GBM in vitro, markedly attenuated in the presence of EACA (P<0.0005) and, to a lesser extent, by addition of aprotinin (P<0.01). The activity of elastase was significantly reduced in glomeruli of nephritic rats treated with EACA or aprotinin (both P<0.001), while activities of remaining proteinases were not appreciably affected. The beneficial influence of proteinase inhibitors on rat anti-GBM disease may be due, at least in part, to abrogation of superoxide generation in nephritic glomeruli. EACA and aprotinin also have potential to interfere with digestion of GBM, and both these effects may be related to suppression of glomerular elastase.     

Myopathy in Chronic Renal Failure

A group of eleven patients in end-stage renal failure who developedproximal weakness is described. The muscle weakness in all caseswas shown to be myopathic in nature by quantitative electromyography.Four of the patients presented with muscle dysfunction and werefound to have severe osteomalacia secondary to renal disease.In these patients vitamin D in high doses produced some improvementin muscle weakness. In the other patients who were on maintenancedialysis, muscle weakness improved dramatically after renaltransplantation or dialysis with deionized water. There wereno quantitative differences between the two groups as far asmuscle weakness was concerned. However it is suggested thatmetabolic bone disease may be one pathogenic factor in the firstgroup and that some aspect of renal failure per se (or its treatmentby dialysis) may predominate in the second and contribute tothe first. ¹Present address: Medical School, Northwestern University, 303East Chicago Avenue, Chicago 60611, Illinois, U.S.A. ²Present address: Department of Neurology, Wayne State UniversityMedical School, Detroit, Michigan 48092, U.S.A.     

Changing Pattern of Acute Renal Failure

During the four-year period 1981–1984, 250 patients withsevere acute renal failure were treated at one centre. Therewere seven obstetric cases (2.8 per cent) 118 ‘surgical’cases (47.2 per cent) and 125 medical cases (50 per cent). Thisis a different pattern from that seen in the majority of earlierreports. In 60 of the 125 medical patients the aetiology ofthe acute renal failure could only be determined by renal biopsy.This series suggests that with changing medical practice (particularlythe improvement in resuscitation) and an ageing population,the pattern of causes of acute renal failure is altering. Italso highlights the value of renal histology as a guide to diagnosisand treatment in patients with unexplained acute renal failure. ^* Present address: The General Infirmary at Leeds, Great GeorgeStreet, Leeds LSI 3EX. Present address: Royal Victoria Infirmary, queen Victoria Road,Newcastle upon Tyne NE1 4LP     

Wilson's Disease in the United Kingdom and Taiwan: I. GENERAL CHARACTERISTICS OF 142 CASES AND PROGNOSIS * II. A GENETIC ANALYSIS OF 88 CASES

I. General characteristics and prognosis with penicillaminetherapy were analysed in 142 patients with Wilson's diseasefrom the United Kingdom and Taiwan. Wilson's disease has genetic heterogeneity with variations inclinical symptomology between individual families as well asbetween races and countries. Chinese females had an early onsetof symptoms (mean 11.8 years) and death (mean 13.9 years, whereasChinese males had a later onset (mean 20.9 years) and age atdeath (mean 23.2 years). The British patients showed a similartrend, with females having an earlier age at onset of symptomsthan males. Males in predominantly female affected familiesusually had an early onset, whereas females in predominantlymale affected familes had a late onset of symptoms. Twenty-fiveof 30 patients with an onset of symptoms at age 20 or laterwere male. There were more females than males in the 55 Chinesecases (25 M., 30 F.), whereas there was a predominance of malesin the 87 British cases (50 M., 37 F.). Response was good to penicillamine therapy given for periodsof up to 16 years in 88 patients with adequate follow-up. Seventeenwere asymptomatic at diagnosis. Sixteen of these have been treatedwith penicillamine, all but one of whom remain alive and asymptomatic.Of 36 symptomatic patients who did not receive penicillaminetherapy, 35 are now dead. Thirty-one of the 35 symptomatic patientstreated with penicillamine are now alive and 18 of these arenow asymptomatic. Three nonresponders who were studied had renaltubular acidosis, a poor prognostic finding. ¹Present address: U.S. Naval Medical Research Institute, NationalNaval Medical Center, Bethesda, Maryland 20014, U.S.A. ²Present address: Gastroenterology Unit, Prince Henry Hospital,Sydney, Australia. Formerly Will Edmond Fellow of the RoyalCollege of Physicians of London in the Department of Medicineof the Royal Free Hospital. ³Department of Statistics, London School of Hygiene and TropicalMedicine.     

Proteinuric renal disease in children in South-Western Uganda

Sir, Proteinuric renal disease is common in Africa in both childrenand adults: in the 1960s it accounted for 2–3% of medicaladmissions.¹ The condition is more severe than nephrotic syndromein developed countries, incurring high mortality and typicallybeing resistant to corticosteroids or antimitotic agents. Admissionrates with nephrotic syndrome are higher during periods of intensemalaria transmission, and an     

Renal Disease in Essential Mixed Cryoglobulinaemia: LONG-TERM FOLLOW-UP OF 44 PATIENTS

The mode of presentation of renal disease in 44 patients withessential mixed cryoglobulinaemia (EMC) was: acute renal failure(two patients), acute nephritic syndrome (six patients), nephroticsyndrome (eight patients), proteinuria and/or haematuria (28patients). Renal biopsy, performed in 35 patients, showed proliferativelesions in 33, while only minimal glomerular changes were seenin the remaining two. Immunofluorescence studies showed: IgG(85 per cent), IgA (36 per cent), IgM (90 per cent), C3 (90per cent), Clq (47 per cent), and C4 (33 per cent) deposits,mainly located in subendothelial position. On electron microscopy,crystalloid structure of deposits and monocyte infiltrationof capillary loops were the outstanding feature. The survivalrate was 75 per cent at 10 years from the onset of clinicalsymptoms. Thirty-nine patients were followed for three to 146months (mean 53·8). Twelve patients died, cardiovasculardisease and infection being the commonest cause of death. Thirteenpatients showed acute renal failure or acute nephritic syndrome:nine recovered completely, whereas the remaining four died duringthe acute renal episode. Three patients developed chronic renalfailure, but only one required chronic dialysis. The ominoussignificance of renal impairment in EMC should therefore berevaluated. The high prevalence of hypertension (28/44 patients)which was refractory to treatment in six, may be important tothe clinical outcome.     

中西医结合治疗老年性肾炎性肾病综合征临床观察

目的:探讨中西医结合治疗与单纯西药治疗老年性肾炎性肾病综合征临床疗效。方法:40例患者随机分为治疗组(中西医结合组)和对照组(药物治疗组)。结果:治疗组完全缓解率和总有效率为57.2%和90.5%,显著高于对照组的21.0%和57.8%,(P <0.05);而治疗组复发率仅5.3%,明显低于对照组的45.5%,(P <0.05)。结论:中西医结合治疗老年性肾炎性肾病综合征疗效明显优于单纯西药治疗组。     

Familiar Hyperkalaemic Acidosis

We evaluated a 26-years-old man with hyperkalaemic acidosis,apparently inherited as an autosomal dominant trait. Type IIpseudohypoaldosteronism was suggested by normal aldosteroneproduction and renal sodium conservation. The cause of acidosisin this syndrome is unknown. Both urinary ammonium excretionand bicarbonate threshold were low during hyperkalaemia. Aftercorrecting the hyperkalaemia ammonium excretion was normal,but bicarbonate threshold remained low. Maximum bicarbonatereabsorption, urine to blood pCO₂ gradients, and minimum urinepH were normal. These findings suggest that hyperkalaemia mightcontribute to the acidosis by limiting urinary buffer, but thatthe primary defect is reduced mineralocorticoid effect on hydrogenion and secretion. When the poorly reabsorbed anion, sulphate,was infused, hydrogen ion and potassium secretion were normal.When the relatively reabsorbable anion, chloride, was infused,potassium secretion was decreased. Thesefinding suggest thatthe attenuated mineralocorticoid effect on hydrogen ion secretionis due to increased reabsorptive avidity for chloride in thedistal nephron. To determine if this defect caused resistanceto mineralocorticoid we increased mineralocorticoid by dietarysodium restriction and later administered desoxycorticosteroneand fludrocortisone. Both endogenous and exogenous mineralocorticoidcaused increased net acid excretion and corrected the acidosis,indicating no resistance to mineralocorticoid. Hydrochlorothiazide50 mg daily promptly corrected the acidosis and the hyperkalaemiaby increased urinary potassium excretion. We conclude that theacidosis of type II pseudohypoaldosteronism is due in part toattenuation of the voltage-dependent moiety of mineralocorticoid-drivenacidification caused by enhanced distal chloride reabsorption.Suppression of ammoniagenesis by hyperlkalaemia exaggeratesthe acidosis. The acidosis and hyperkalemia are corrected byhydrochlorothiazide. ¹Present address: Department of Medicine, Naval Medical Center,Okinawa The opinions and assertions contained herein are the privateones of the authors and are not to be construed as officialor reflecting the views of the Naval Medical Command or theUnited States Navy. ³Present address: 28 Deerpath Dr.,New Hartford, NY 13413, USA     

Drug Associated Acute Interstitial Nephritis: Clinical and Pathological Features and the Response to High Dose Steroid Therapy

Nine episodes of drug associated acute interstitial nephritis,in seven patients, were treated between 1972 and 1980. The drugsimplicated were cotrimoxazole (three times), ampicillin, Magnapen(amplcillin and flucloxacillin), penicillin, gentamicin, paracetamoland ben-drofluazide. The time from exposure to the onset ofsymptoms ranged from one to 30 days. Presentation was with acuterenal failure, which was non-oliguric in five cases, accompaniedby rash (four), fever (four), and loin pain (two). Renal biopsy was carried out in all cases, and showed a characteristicinterstitial infiltrate comprising substantial numbers of lymphocytesand plasma cells, with a variable number of neutrophils, eosinophilsand histiocytes. Immunofluorescence was negative in all fourcases studied in the acute phase, and showed scattered depositsof IgG, IgM, IgA and C3 on the tubular basement membrane inone patient during recovery. Significant proteinuria and anabnormal urine deposit were present in all cases, and sevenof nine had radiological evidence of enlarged kidneys. Seven episodes were treated with high doses of methyl prednisoloneand in all there was a response with a diuresis or spontaneousfall in serum creatinine within 72 hrs, and recovery of virtuallynormal renal function. Of two cases who did not initially receivesteroids, one improved more slowly and one developed chronicrenal impairment. Present address: Department of Medicine, Charing Cross Hospital,Fulham Palace Road, London W6 8RF.     

Glomerular and tubulointerstitial diseases

This article provides a general overview of some of the more common or illustrative glomerular and tubulointerstitial disorders encountered in clinical practice. Disorders are grouped into those causing the nephrotic syndrome, the acute nephritic syndrome and rapidly progressive glomerulonephritis (RPGN), and chronic tubulointerstitial disease. This division is useful for narrowing the differential diagnosis and deciding on further testing and management. Elements of the past history, including detailed family, medication, and social histories, and recent symptoms and physical examination findings are as much a part of the diagnostic workup as are urinary and blood tests. An assessment of the tempo and severity of renal deterioration is critical to separate potential medical emergencies, such as RPGN, from those more indolent disorders that can be managed by the primary care physician.     

成人肾病综合征31例病理与临床观察

目的　通过 31例成人肾病综合征 (Nephroticsyndrome ,NS)病理与临床观察 ,分析探讨 2 4小时尿蛋白排出量和血肌酐与合并肾小管间质损害的关系。方法　将患者分A组 (无合并肾小管间质损害 ,n =12 )和B组 (合并肾小管间质损害 ,n =19)进行对比分析。结果　NS时肾小管间质病变的发病率相当高 ( 19/31;6 1.2 9% ) ,B组 2 4小时尿蛋白排出量明显高于A组 (P <0 .0 5 ) ,两组血肌酐值差别无显著性意义 (P >0 .0 5 )。结论　大量蛋白尿是NS的最主要临床特征 ,但其除作为一种肾脏损害标志外 ,更是一种促进肾病进展的独立危险因子 ,提示大量尿蛋白对肾小管间质的损害作用     

Hypothalamic-Pituitary-Adrenocortical Suppression and Recovery in Renal Transplant Patients Returning to Maintenance Dialysis

Sixty-six per cent of a group of 21 renal transplant recipientswith chronic renal failure were shown to have adrenal suppressiondue to glucocorticoid treatment. Gradual withdrawal of steroidsin these patients returning to maintenance dialysis therapywas achieved with few symptoms of hypoadrenalism. Adrenal recoveryoccurred in 52 per cent of patients after three months and 71per cent after six months. However, the plasma cortisol responseto insulininduced hypoglycaemia, studied in patients in whomadrenal recovery had been demonstrated, was impaired in 46 percent of cases. These results indicate that corticosteroids inrenal transplant recipients induce profound hypothalamic-pituitary-adrenalsuppression which is slow to recover. Such patients returningto maintenance dialysis are at risk of acute adrenocorticalinsufficiency for several months. Although withdrawal of steroidscan be achieved safely, cover during periods of stress shouldbe given until the hypothalamic-pituitary-adrenal axis has beenshown to respond normally. Present addresses: ^*Stobhill General Hospital, Glasgow Present addresses: Royal Postgraduate Medical School, London.     

Prognostic signs of accelerated progression of nephrotic types of chronic glomerulonephritis

A prognostic value of some clinical and morphological signs was followed up in 43 patients with chronic glomerulonephritis concurrent with the nephrotic syndrome versus 85 with other clinical types of the disease. There was a statistically significant incidence of disease progression in combination with arterial hypertension, resistance of the nephrotic syndrome over 12 months and detection of sclerosing renal glomeruli and interstitium within 2 years after onset of the disease. The protracted course of the nephrotic syndrome is a precursor of occurrence of chronic renal failure. With less prolonged phases of the syndrome there is evidence for a long-term period of functional compensation. Occurrence of arterial hypertension early in the disease, as early renal parenchymal sclerosis, fails to predict the rates of chronic renal failure development. In the absence of these factors, the possibility of prompt disease progression may be rejected in all likelihood.     

Clinical manifestations of APS-nephropathy in primary antiphospholipid syndrome

AIM: To elicit clinical features of nephropathy associated with antiphospholipid syndrome (APSN) in patients with primary antiphospholipid syndrome (PAPS). MATERIAL AND METHODS: The analysis of clinical characteristics and course of APSN has covered 24 patients with PAPS (16 females and 8 males, mean age 34.3 years). Renal damage was represented by arterial hypertension (AH), urinary syndrome, functional decline. All the patients were tested for anticardiolipin antibodies and/or lupus anticoagulant. Renal biopsy was made in 7 patients. RESULTS: PAPS patients developed renal affection in the onset of APS or within the first 5 years of its course. In the majority of patients APSN combined with abnormalities of CNS, heart and skin. Arterial/arteriolar thromboses prevailed. APSN manifested with: AH (n = 23, severe AH in 11), abnormal renal filtration (n = 17, creatinine rise in 8), urinary syndrome with proteinuria (n = 23, in 14 with hematuria). The following clinical variants of APSN were proposed: urinary syndrome with AH (n = 16; 67%), acute nephritic syndrome (n = 7; 29%), nephrotic syndrome (n = 1). Morphological studies of biopsies from APSN patients have revealed sclerotic changes, thrombotic microangiopathy, nonspecific alterations in the glomeruli. CONCLUSION: APSN is a variant of microvascular renal affection caused by thrombotic processes in intra-organ microcirculation. It is an early clinical marker of APS. Clinically, APSN manifests with vascular renal affection, the earliest symptom being inhibition of glomerular filtration. Clinical combinations of the symptoms allow to distinguish variant of APSN suggesting the existence of acute and chronic APSN. Combination of APSN with affection of the CNS, heart and skin points to a special PAPS subtype characterized by generalized ischemic damage to the organs as a result of intraorganic arterial and/or arteriolar thromboses.