Immunotherapy for Alzheimer's Disease: Current Scenario and Future Perspectives.

Alzheimer's disease (AD) is a global health concern owing to its complexity, which often poses a great challenge to the development of therapeutic approaches. No single theory has yet accounted for the various risk factors leading to the pathological and clinical manifestations of dementia-type AD. Therefore, treatment options targeting various molecules involved in the pathogenesis of the disease have been unsuccessful. However, the exploration of various immunotherapeutic avenues revitalizes hope after decades of disappointment. The hallmark of a good immunotherapeutic candidate is not only to remove amyloid plaques but also to slow cognitive decline. In line with this, both active and passive immunotherapy have shown success and limitations. Recent approval of aducanumab for the treatment of AD demonstrates how close passive immunotherapy is to being successful. However, several major bottlenecks still need to be resolved. This review outlines recent successes and challenges in the pursuit of an AD vaccine.

Pathogenesis of membranous nephropathy: update.

Membranous nephropathy (MN) is the most common cause of adult nephrotic syndrome and it accounts for about 25% of renal biopsies done for this syndrome. Most of the cases are primary or idiopathic in nature while only about one third of the cases are secondary to some known disease.This review describes the recent advances regarding pathogenesis. Membranous nephropathy is an organ specific autoimmune disease. Experimental studies in late 1950s using rat models (Heymann Nephritis) has provided much understanding of pathogenesis of the disease. Role of in situ formation of immune complexes and involvement of complement system was established. Recently the M-type phospholipase A2 receptor (PLA2R) has been identified as target antigen in humans. High titre anti-bovine serum albumin antibodies have been found in children with this disease. It is hoped that in near future non invasive diagnosis and individualised therapy may become a reality.

Spectrum of renal lesions in HIV patients.

BACKGROUND: A variety of renal lesions have been reported in HIV positive patients from western world however there is paucity of Indian data. METHODS: Over a four year period, all hospitalised HIV positive patients were screened for renal involvement. Screening was done with urinalysis. Those with abnormality in urine examination underwent further assessment with clinical, biochemical, immunological profile and renal biopsy. Renal histology was studied by light and electron microscopy. RESULTS: Twenty-five (17.6%) of the 142 patients screened, had proteinuria/abnormal urinary sediment however none of the patient had proteinuria in nephrotic range. Fourteen of these 25 patients were asymptomatic while others had AIDS. Renal biopsy was studied by light microscopy in all and by electron microscopy in 11 cases. On histology mesangioproliferative GN was encountered in eight, focal segmental glomerulosclerosis in four and collapsing GN in one patient. In two cases cryptococcal infiltration and in one lymphomatous deposits were seen in glomerulus and interstitium. In one patient interstitium showed granulomas and in other three mononuclear cell infiltration. Histology was normal in 8 (32%) patients. On EM visceral cell hyperplasia and vacuolisation was seen in all, two had collapse of glomerular basement membrane and in three cases tubuloreticular structures were seen. There was no co-relation of renal histology with duration or severity of the disease (p > 0.05). No deterioration of renal function was seen over a short follow up period of 4.2 months (1-20 months). CONCLUSION: This study highlights that HIV patients exhibiting abnormal urinary sediment usually have underlying renal lesion and at times unexpected opportunistic infections may be present.

Hypochromic anaemia in chronic renal failure--role of aluminium.

BACKGROUND: Anaemia is a cardinal feature of chronic renal failure and classically it is normochromic normocytic. Hypochromic anaemia in these patients is often attributed to iron deficiency. AIM: This study was aimed to find the contribution of aluminium in causation of anaemia in CRF patients. METHODS: Dialysis dependent patients of chronic renal failure with adequate dietary intake (> 1500 Cals/day) and no apparent source of blood loss were evaluated for type of anaemia. (During period of this study centre didn't have reverse osmosis plant for water treatment). Evaluation included upper GI endoscopy, complete hemogram, serum proteins, serum iron, total iron binding capacity, and bone marrow iron status. For aluminium evaluation serum aluminium levels were done. RESULTS: Sixty-four patients were evaluated for type of anaemia. Mean age of patients was 41.19 years (15-76 years) with male:female ratio 2.3:1. Classical normochromic picture was seen in 28.5% while rest had hypochromic picture. On bone marrow aspiration study two patients had zero iron stores while all others had normal/excessive iron stores. In 10 patients with hypochromic picture, mean serum aluminium levels were 170 micrograms/L (30-310 micrograms/L). CONCLUSIONS: This study highlights the high prevalence of hypochromic anaemia in patients with adequate dietary intake and aluminium overload in Indian CRF patients.

Efficacy of enalapril in the treatment of steroid resistant idiopathic nephrotic syndrome.

Fifteen patients of idiopathic nephrotic syndrome who failed to respond to 8 weeks of corticosteroid therapy formed the material for this study. There were 10 males and 5 females, age ranging from 4 to 56 years. Three patients had hypertension. Histological lesions were focal and segmental glomerulosclerosis (FSGS) in 8; membranous glomerulonephritis in 3; mesangial proliferative glomerulonephritis in 2 and membranoproliferative glomerulonephritis in 2 patients. Proteinuria ranged from 3.64 to 8.66 g/1.73 m2/day. Serum albumin ranged between 2.2 to 3.3 g/dl. Serum creatinine was elevated > 1.5 mg/dl in 3 cases. After discontinuing steroids, enalapril was started in a dose of 2.5 mg/day and increased by 2.5 mg/day every 3-4 days till the maximum tolerated dose but not exceeding 20 mg/day. Proteinuria, serum albumin and serum creatinine estimations were done every 4 weeks for six months and every three months thereafter. Patients were followed up for 6 to 30 months. Proteinuria decreased to < 1.5 g/1.73 m2/day in 12 patients (80%) and to < 0.5 g/1.73 m2/day in 10 patients (66.7%) by 8 weeks. There was no significant decrease in proteinuria in 3 (20%) patients; two of these were cases of FSGS and one of membranoproliferative glomerulonephritis. Oedema, hypoalbuminaemia and hypercholesterolaemia returned to normal in all patients who had a decrease in the proteinuria. There was no correlation between the histological lesion and response to enalapril. There was no rise in the serum creatinine level above the baseline in any of the patients. Except for cough in one patient, no other significant side effects were observed. We conclude that enalapril is effective in reducing proteinuria and thereby the morbidity in steroid resistant nephrotic syndrome irrespective of the underlying pathology.

LUPUS NEPHRITIS-A CRITICAL ANALYSIS OF 17 PATIENTS.

Over a 3 year period from June 94 to June 97, out of 28 patients of systemic lupus, 17 were diagnosed as renal lupus. Demographic data showed 12 females and 5 males, mean age being 32.2 years (range 12 to 54 years). Mean time gap between presentation and definitive diagnosis was 32.4 days (7 days to 5 years). 2 patients (11.76%) presented renal lupus, one (5.88%) with acute interstitial lung disease and the remaining had the usual systemic manifestations of lupus. Anti dsDNA antibodies were positive in all patients while ANA was negative in 3 cases. Renal involvement consisted of rapidly progressive glomerulonephritis in 2 patients (11.76%), nephrotic syndrome in 4 (23.52%) and non nephrotic range proteinuria in 11 (64.70%) patients. Mean serum creatinine at presentation was 2.4mg/dl (0.8mg/dl to 8.9 mg/dl). Three patients were dialysis dependent. Renal histology on light microscopy comprised of class II lesions in one (5.88%), class III in 4 (23.52%), class IV in 11 (64.70%-including one with crescents) and class V in one (5.88%) patient. All patients with advanced class III/IV lesions were treated with corticosteroids and cyclophosphamide pulses. Except one patient who died of pyopericardium all others improved and their serum creatinine stabilised around 2.3 mg/dl (0.8 to 4.6 mg/dl). The study highlights the importance of early diagnosis and aggressive management in this potentially treatable disease.

UPPER GASTROINTESTINAL MUCOSA IN CHRONIC RENAL FAILURE - AN ENDOSCOPIC AND HISTOLOGICAL EVALUATION.

Over a three year period, 98 patients of moderate to severe chronic renal failure (S creatinine > 5 mg/dl) admitted in our centre were evaluated for upper GI lesions. All patients underwent upper GI endoscopy. In 68% upper GI mucosa was affected. Various lesions encountered were gastritis (25.5%), duodenitis (10.2%), gastroduodenitis (21.4%), telengiectasia (5.1%), and peptic ulcer in 6.1%. In 74 patients three biopsies, one each from antrum, fundus and duodenum were taken. 45.9% of these had chronic gastritis and 14.8% chronic duodenitis. Prevalence of H pylori on histology was 17.56%. 20 patients (9.6%) developed upper GI bleed during hospitalisation. In 17 (85%) patients, where endoscopy could be done, gastritis/duodenitis/oesophagitis were the common underlying lesions.

SPECTRUM OF ACUTE RENAL FAILURE IN A SERVICE HOSPITAL.

A prospective study of 82 patients with acute renal failure was carried out over the last 2 years. Mean age of the patients was 35.6 years (8-82 years). Male to female ratio was 3.5:1. The etiological factors were septicaemia in 18 patients (21.95%), aminoglycoside toxicity in 16 patients (19.51%), open heart surgery in 8 patients (9.76%), volume depletion and blood loss in 12 patients (14.63%), glomerulonephritis in 4 patients (4.88%), renal allograft dysfunction in 4 patients (4.88%), and miscellaneous causes in 20 patients (24.39%). Non-oliguric renal failure was observed in 39.02 per cent cases. Dialysis support was required in 65.8 per cent of the cases; with average 5.6 (4 to 11) dialysis sessions. Four patients of acute renal failure following open heart surgery were given continuous arterio-venous haemofiltration. Overall mortality was 32.5 per cent, septicaemia accounting for 60 per cent of the deaths.

CHRONIC RENAL FAILURE - PITFALLS IN DIAGNOSIS.

Chronic renal failure means progressive and irreversible destruction of nephrons involving almost every organ system of the body. Early diagnosis of the disease and conservative therapy can slow down progression towards end stage renal disease. Nocturia/polyuria, anaemia, hypertension, osteodystrophy, reduced kidney size and associated acute renal failure are features which help physician in an early diagnosis. Detailed evaluation of these features has been suggested.

AZATHIOPRINE INDUCED BONE MARROW SUPPRESSION IN LIVE RELATED RENAL ALLOGRAFT RECIPIENTS.

Over a follow-up period of 6 years, 4 out of 31 live related renal allograft recipients (12.9%) developed azathioprine induced bone marrow suppression. Presentation in 3 patients was with fever and 2 patients also had associated graft dysfunction. All patients had leucopenia, 2 patients in addition had anaemia and one patient had pancytopenia. Bone marrow suppression developed 9.6 months (3.5-16.0 months) following transplantation and recovery followed over a period of 30 (18-49 days) days after withdrawal of the drug. One patient succumbed during the phase of bicytopenia.