KEY WORDS

HIVAN, Nephrotic Syndrome, MPGN

INTRODUCTION

HIV disease usually presents with the classical features of AIDS and opportunistic infections. In literatures, presentation of anasarca is sparing reported. HIV associated Nephropathy (HIVAN) is one of the leading causes of ESRD among HIV infected patients. HIVAN is characterised by heavy proteinuria and impairment of renal function. HIVAN could be an early manifestation of HIV infection. The term HIVAN is reserved for the characteristic light microscopic pattern of FSGS with collapsing feature and related mesangiopathies¹.  Here we are reporting a case presented with anasarca, an uncommon presentation of HIV associated nephropathy.

CASE REPORT

A 24 year old male came to the outdoor department with complaints of progressive generalized swelling for 20-25 days. There was no history of fever, decreased urine output, jaundice, rash, oral ulcers, sore throat, arthralgia, hematuria, blood transfusion or recent vaccination.

On examination, the blood pressure was 170/100 mm Hg and pulse rate was 88 per minute. The patient was having pallor and generalized swelling (pitting type), without lymphadenopathy or icterus. Chest, cardiovascular and neurological examination was normal. On abdominal examination, distended abdomen and mild hepatosplenomegaly was present. His investigations revealed Hb was 8.8 gm/dl, total leucocyte count was 6900/mm3 (P-40, L-46, E-12, M-2), platelet count was 1.78 lakh/mm3, blood urea was 75 mg/dl and serum creatinine was 2.2 mg/dl. On urine examination, albumin was 4+, RBCs: 20-30 per high power field, 2-3 pus cells/HPF and granular and hyaline casts were present. Total serum proteins were 4.2 gm/dl with both albumin and globulin being 2.1 mg/dl each. Serum cholesterol was 310 mg/dl. ASO titre was negative at the time of admission and after one week. LFT, thyroid function test and serum electrolytes and blood sugar levels were found to be normal. Chest X-Ray was normal. USG Abdomen showed bilaterally enlarged kidneys with the right kidney being 151 X 67 mm and left kidney being 155 X 75 mm, hepatosplenomegaly and mild ascites. On further investigations, C3 complement levels was low (<0.30 gm/dl) and C4 was normal. 24 hours urinary protein was found to be 17.8 grams. The patient was found to be HIV-1 positive by ELISA and his absolute CD4 count was 301. HBsAg and Anti HCV were negative. Renal biopsy was done with universal precautions and on light microscopy Membranoproliferative Glomerulonephritis (MPGN) was diagnosed.

The working diagnosis was kept as Immunocompromised state presented with Anasarca cause Nephrotic Syndrome (MPGN).

The patient was treated conservatively with salt and fluid restriction along with anti hypertensives, diuretics and ACE inhibitors. The patient was put on corticosteroids (prednisolone 1mg/kg daily) and anti retroviral therapy (ART) after the biopsy report. On follow up after one month, his anasarca had subsided and the patient was asymptomatic. His 24 hour urine protein had decreased to 7.5 gm/dl. Now the patient is on ART and tapering dose of steroids over 2-3 months, and is in regular follow up after every 15 days.

DISCUSSION

Renal involvement in a patient infected with HIV may include glomerulonephritis, tubule interstitial disease, acute tubular necrosis, drug related interstitial nephritis, pyelonephritis, nephrocalcinosis, electrolyte abnormalities, neoplasms (Kaposi’s sarcoma and lymphoma) and opportunistic infections (such as aspergillosis, mucormycosis and adeno virus infections)².

The classic and the most common HIV associated glomerulopathy is an aggressive form of focal segmental glomerulosclerosis, an entity that is termed as HIV associated nephropathy (HIVAN). This disease may be the first manifestation of infection in anotherwise asyptomatic patient³. Renal biopsy typically reveals visceral epithelial cell swelling, collapse of the glomerular capillary tuft, severe tubule-interstitial inflammation, and microcystic dilatation of renal tubules. The presence of tubuloreticular inclusions and the aggressive clinical course distinguish HIVAN from idiopathic focal segmental glomerulosclerosis. The mechanisms of renal cell injury are still being defined. Viral DNA has been demonstrated in the renal epithelia of HIV infected patients with or without nephropathy, suggesting that pathogenic factors, other than the infection of cells, are required for the induction of disease. In HIV infection, about 73% are focal segmental glomerulosclerosis (HIVAN), about 10% are membranoproliferative glomerulonephritis (MPGN), 6% are minimal change disease, 5% are membranous nephropathy. IgA nephropathy and mesangioproliferative nephropathy make up the remaining fraction¹. There is strong predilection for HIVAN among black HIV infected patients. The black:white ratio among patients with HIVAN is 12:1⁴. Blacks were also more likely to have more severe clinical renal disease with heavier proteinuria and higher incidence of nephrotic syndrome and associated renal insufficiency.

Racial factors are also important as they are involved in the mutation of HIV receptors, which may in part; explain some differences in the racial predisposition to HIV infection to HIVAN. Although intravenous drug use has been the most common risk factor for HIVAN, the disease has been seen in all groups at risk for acquired immunodeficiency syndrome (AIDS) including homosexuals, those with perinatally acquired disease, heterosexual transmission and exposure to contaminated blood products. HIVAN usually occurs in patients with a low CD4 count, but full blown AIDS is not a pre requisite for the disease. In one New York study, the onset of HIVAN was most common in otherwise asymptomatic HIV infected patients (12 out of the 26 were asymptomatic patients). There is no relationship between the development of HIVAN and the patient age, duration of HIV infection or the presence or absence of other opportunistic infections.

The clinical features of HIVAN include the presenting features of proteinuria (typically in the nephrotic range) and renal insufficiency. Other manifestations of the nephrotic syndrome including oedema, hypoalbuminemia and hypercholesterolemia have been common. The sonographic evaluation may reveal enlarged kidneys. The clinical course in most patients is marked by progression to ESRD within weeks to months.

MPGN may be the most common pattern of immune complex mediated glomerulonephritis seen in HIV infected patients⁵. Membranoproliferative glomerulonephritis is a pathologic term characterised by thickening of the glomerular basement membrance, proliferation of mesangial cells and influx of mononuclear inflammatory cells. This disease is often the result of immune complexes. Immune complex disease associated with hepatitis C virus (HCV) co infection is the most common cause of membranoproliferative glomerulonephritis in HIV-1 infection.

Renal function in some patients has been reported to improve dramatically in response to treatment with corticosteroids, but this is not predictable and carries significant risk⁶. At present the therapy of HIVAN should include the same anti retroviral therapy as the patients without nephropathy. ACE inhibitors have been shown to decrease the proteinura in HIVAN and to slow the progression to renal failure. Renal transplantation is a viable option in selected patients⁷.

Our patient of nephrotic syndrome was diagnosed to be MPGN, which can be the initial manifestation of HIV infection. Therefore we suggest that in an unexplained case of nephrotic syndrome in an adult, the HIV status should be checked.

 BIBLIOGRAPHY

1. D’Agati V, Appel GB: Renal pathology of human immunodeficiency virus infection. Semin Nephrol 18:406-421, 1998
2. Rao TKS, Freidman EA, Nicastri AD: the types of renal disease in acquired immunodeficiency syndrome. N Eng J Med 1987; 316: 1062-1068
3. Hugh R Brady, Yvonne M, O’ Meara, Barry M, Brenner: Glomerular disease in Dennis L Kasper (edi) Harrison’s Principles of Internal Medicine, 18^th ed
4. Bourgoigine JJ, Ortiz-Interian C, and Green DF: The human immunodeficiency virus epidemic and HIV associated nephropathy. In Hatano M (ed): Nephrology, Tokyo, Springer-Verlag 1990, pg 484-492
5. Appel, Radha Krishnan and D’Agati: secondary glomerular disease. In Barry M. Brenner (ed). Brenner and Rector’s The Kidney, 7^th edition, Saunders, 2004 print, pg 1381-1447
6. Smith MC, Pawar R, Carey JT et al: Effect of corticosteroid theraoy on human immunodeficiency virus associated nephropathy. Am J Med 97; 145-151, 1994
7. Jonathan A Winston, Paul E Klotman: Renal disease. In Raphael Dolin, Henry Masur, Micheal S. Sarg (ed) AIDS therapy, 2^nd edition, Churchill Livingstone 1999: pg 853-859