Glomerulonephritis presenting as acute renal failure.
Oliguric acute renal failure (ARF) occurs in 5% of hospitalised patients with acute glomerulonephritis (AGN). Almost any type of glomerular disease may present as, or be complicated by ARF, yet the ultimate outcome of a given case, in this heterogenous group would depend upon the age of the patient, the etiology and histology of the glomerular disease. The effect of these variables on the outcome of the disease is studied here.
Fifty cases who were diagnosed to have GN on clinical evaluation, laboratory analysis and where available, histopathology were studied. Only those patients of GN who developed oliguria (urine output less than 400 ml/day) and acute azotemia (rise of plasma creatinine by more than 0.5 mg/day) were included in the study. A detailed clinical evaluation was done to detect the cause of GN. Apart from urinalysis, the laboratory investigations included plasma urea nitrogen, creatinine, proteins, electrolytes, complement and immunoglobulins. Secondary glomerular diseases were detected by doing anti-streptolysin 'O' titres, antinuclear antibody, anti-double stranded DNA antibody and circulating immune complexes. Light microscopic evaluation of histological material was done whenever available, with the help of percutaneous renal biopsy or at autopsy. Therapy was individualised. Both primary and secondary GN with extensive crescents were treated with 'quadruple' therapy comprising steroids (1 mg/kg/day), cyclosphosphamide (2.5 mg/kg/day), aspirin (300 mg/ day), dipyridamole (10 mg/kg) and heparin 500 U/kg/day. Membrano-proliferative GN was treated with steroids (2 mg/kg on alternate days) and if there was no response in two months, eyclophospharnide was added. Diffuse proliferative lupus nephritis was treated with steroids (1 mg/kg/day) and if required with cyclophosphamide.
Both hemo and/or peritoneal dialysis was carried out whenever indicated. Improvement was defined as significant improvement in renal function so that dialysis was no longer required.
The age and sex distribution was as shown in [Table 1]. A preceding history of infection was available in 16 patients including 8 cases of documented beta hemolytic streptococcal infection [Table 2]. Four cases of systemic lupus erythematosus (SLE) and one each of Henoch-Schonlein purpura (HSP) and hypersensitivity vasculitis were the other secondary causes of GN.
Plasma creatinine values ranged from 2 to 12 mg% and correlated positively with survival. Twenty-five patients wherein the highest creatinine values attained were less than 4 mg% had a survival of 84% as compared to only 44% survival in patients with creatinine values exceeding 4 mg%.
Histology was available in 40 cases and proliferative glomerulonephritis was the feature in 38 of them.
Epithelial crescents were seen in 19 patients (42.5%). Glomerular sclerosis (14), interstitial edema (11), interstitial infiltration (13), tubular atrophy (15) and tubular necrosis (2) were the other changes observed. The 13 patients of post-infectious GN who could be studied histologically, revealed diffuse exudative proliferative GN and in 5 patients there were crescents involving 30-80% of glomeruli. The 4 patients of SLE revealed DPLN histology (W.H.O. type IV). The patients of H.S.P. and vasculitis revealed changes of focal proliferative GN and mesangial proliferation respectively. Of the 21 patients with idiopathic GN, extracapillary GN (7), crescentic MPGN (12 including 7 patients with crescents) and nil disease (2) were histblogical type encountered.
The outcome of renal failure varied. Thirty-two patients (64%) showed significant improvement in renal function as seen in [Table 2]. Secondary GN (82% survival) fared better than idiopathic GN (50% survival). Young children (<10 years) had better survival compared to older patients [Table 1]. Histologically, extracapillary-crescentic GN had the worst prognosis as seen in [Table 3].
Glomerulonephritis (GN) and vasculitis may present as ARF. Although fever, extra-renal systemic manifestations and a nephritic urinary sediment may help differentiate them from other common causes of ARF, a kidney biopsy may be required in doubtful cases. Chugh et al have reported a 9.8% incidence of ARF due to glomerular diseases.
Prolonged oliguria in a patient of AGN is an ominous sign occuring in 5-13% of all hospitalised patients of AGN., The age of the patient, etiology of glomerular disease and the histopathology, determine the outcome of such cases. As seen in our study, children with oliguric AGN have a better prognosis. This is explained by the greater prevalence of post infectious GN in the pediatric age group, a combination which carries a better prognosis.
A preceding history of infection is obtained in ? to ½ of oliguric AGN patients analysed. Harrison et al revealed a much higher survival of 52% in the post-infectious group of GN, compared to a 12.5% survival in another group of oliguric AGN without a post-infectious etiology. A post- infectious etiology was encountered in 32% of our cases and an eighty per cent improvement in this group is in striking contrast to only 50% improvement in primary glomerular diseases. Although 50% of patients of post-streptococcal GN (PSGN) are reported to have reduced renal function as a result of diffuse exudative proliferative GN, fewer than 5% of these patients have oliguria lasting for more than 9 days. Anuria as well as prolonged oliguria carry a bad prognosis and are usually associated with extensive epithelial crescents as was seen in 5 of our patients with PSGN. Spontaneous recovery can occur in as high as 50% of patients of PSGN with crescents. Two such patients in our study improved, albeit with treatment.
Diffuse proliferative lupus nephritis (DPLN), the commonest morphological type of renal involvement is associated with reduced renal function in 75% of cases, at presentation. The long term prognosis of such patients has improved considerably over the years and a 80% 5 year survival rate is reported by most centres. Three of the 4 patients of DPLN in our study, improved with therapy.
Primary glomerulopathies characterized by proliferation of cells in the glomerular tuft can cause ARF by sharply reducing the renal blood flow. All but two of our patients had this mechanism operative in the causation of ARF. Associated tubulo-interstitial changes of tubular atrophy, interstitial fibrosis and infiltration also contribute to renal failure. Hypovolemia, diuretic nephrotoxicity, renal vein thrombosis and secondary acute tubular necrosis (ATN) are the other reasons for azotemia in patients with GN. Two of our patients with 'nil' disease developed secondary ATN and renal failure.
Patients with a clinical syndrome of rapidly progressive GN (RPGN) often, but not invariably, reveal extensive epithelial crescent formation. Therefore, pathological terms like cresentic GN should be avoided, as diffuse endocapillary proliferation, necrotising GN or tubulo-interstitial damage secondary to GN may present as RPGN.4 Only 50% of our patients with oliguric AGN due to primary glomerular disease had extensive crescents in their histology. Membranoproliferative GN (MPGN) which forms 5-10% of all primary glomerulopathies in adults may present with azotemia in roughly 20% of patients. Epithelial crescents may be present in 10% of biopsies of MPGN, and when extensive, carry a bad prognosis. Seven of the 12 patients of MPGN who presented with ARF had crescents involving 30-80% of glomeruli of which 4 patients with extensive crescents involving more than 60% of the glomeruli succumbed, while others improved with treatment.
Extracapillary crescentic GN refers to idiopathic diffuse crescentic GN in which more than 70% of glomeruli reveal crescents alongwith glomerular tuft hyper cellularity without evidence of preceding infection or multisystem disease. The prognosis is bleak and more than 90% need active treatment such as dialysis. Treatment has to be instituted early before the onset of severe azotemia or oliguria. The seven cases in our series were oliguric, severely azotemic and hence had a fatal illness. Intensive therapy with plasmapheresis coupled with steroids, methyl prednisolone 1 gm (I.V. infusion) and cytotoxic drugs has helped in improving the prognosis in these cases.
Thus, amongst the patients in this study, two factors dictated the outcome viz. the etiology and the histology. Determinable causes of renal involvement (secondary glomerular diseases) had a better outcome. The presence of an idiopathic extracapillary crescenting GN meant high mortality.