Case of the Month 16: HIV-associated Nephropathy

Well, Winter is finally here! And with it is the answer to December’s Case of the Month!

Click here to see the initial vignette.

To recap the case, the patient is a a 37 year-old obese man with a past history of MI, CHF, OSA, CKD, and HTN who presents with progressive exertional dyspnea, orthopnea, and bilateral lower extremity edema. His exam is notable for bibasilar crackles, and labs are notable for anemia, leukopenia with elevated protein, mild hypoalbuminemia, Creatinine > 4, proteinuria, and elevated BNP. Bedside sonogram shows bilateral B-lines.

Clinically the patient is demonstrating signs of fluid overload with symptoms of orthopnea, progressive exertional dyspnea, exam with lower extremity edema, and diagnostic studies demonstrating elevated BNP and bilateral B-lines. Although the bedside sonogram did not include an assessment of cardiac contractility, he does have a previous history of an MI and is on dual antiplatelet therapy. However, there are likely multiple factors in play here. It would be odd for a patient of this age to have such advanced CKD simply due to hypertension. Previously noted on labs are the elevated protein with hypoalbuminemia (a “protein gap,”) proteinuria, and leukopenia.

A protein gap (elevated total protein to albumin ratio), is also commonly referred to as a globulin gap in that an assay of serum protein is measuring serum albumin plus serum globulins. A protein gap therefore reflects a relative abundance in globulin concentration, and is commonly associated with malignant processes such as multiple myeloma and other plasma cell dyscrasias like MGUS or Waldenstrom’s macroglobulinemia, or autoimmune disorders. The work-up for a protein gap is pretty involved and includes such tests as a SPEP/UPEP and bone marrow biopsy, and is beyond the scope of management in the ED.

However, the one test that could be performed in the ED that would clarify the etiology of this patient’s renal dysfunction is…an HIV test.

HIV is known to cause hyperproduction of globulin proteins, and though the exact mechanism is unclear, the thought is that HIV infection both directly and indirectly, through various signaling pathways, affects B cell antibody production. And as people may remember from studying for Step 1 or 2 (or 3?), HIV is one of the causes for focal segmental glomerulosclerosis (FSGS), a subset of nephrotic syndrome. Recall that, apart from the obvious effects on the immune system and the increased susceptibility to opportunistic infections, HIV infection has widespread effects on numerous organ systems. It confers an increased risk of cardiovascular death and may cause renal failure as noted above, causes increased bone loss through promoting osteoclast activation and osteoblast apoptosis, increases risk for dementia and other neurocognitive disorders via direct infection within CNS and subsequent apoptosis, malignancy such as primary CNS lymphoma, and hematologic abnormalities like hypercoagulability (keep in mind when applying Wells criteria!), anemia, and thrombocytopenia.

Before the advent of highly active anti-retroviral therapy (HAART), a diagnosis of HIV-associated nephropathy (HIVAN) on renal biopsy meant a likely inevitable decline towards ESRD within a matter of months. HAART has changed everything. Early reports demonstrated histologic recovery within 4 months of HAART, and subsequent observational studies have suggested that continuous HAART as a key factor in preventing HIVAN and the need for hemodialysis. Other observational studies have also shown that use of ACE inhibitors may also slow the decline towards ESRD, though these studies were limited by a small sample size.

Back to our patient: In the ED he was diuresed with IV furosemide 80 mg with symptomatic improvement and admitted. His official echo showed a LVEF of 40%, he underwent continued diuresis that was augmented by metolazone. His other heart failure [Carvedilol, Isosorbide dinitrate, hydralazine] and antihypertensive [Amlodipine] medications were continued. Records were obtained from the outside hospitals that indicated patient had already been worked up plasma cell dyscrasias. Given his elevated creatinine, renal was consulted and upon their recommendation, an HIV test was ordered for the patient. It was positive. His CD4 was 350, and his viral load was 15000.

Despite the fairly advanced nature of his kidney disease, he never fully progressed to ESRD during his hospitalization. He eventually ended up being discharged home with renal, cardiology, and ID follow-up, and was started on HAART soon after his discharge. As of now, about six weeks after his initial admission, his renal function has remained stable.

Stay warm!

References

De Milito Et al. Mechanisms of hypergammaglobulinemia and imnpaired antigen-specific humoral immunity in HIV-1 infection. Blood. 2004. 2180 – 2186

Barbaro. Cardiovascular Manifestations of HIV Infection. Circulation. 2002. 1420- 1425

O’Connell et al., Understanding and Interpreting Serum Protein Electrophoresis. American Family Physician. 2005. 105 – 112

Griswold and Tungsiripat. HIV for the Primary Care Physician. Cleveland Clinic Center for Continuing Education. 3/2016 (Web)

Choi, A., & Rodriguez, R. (2008, January). Comprehensive, up-to-date information on HIV/AIDS treatment and prevention from the University of California San Francisco. http://hivinsite.ucsf.edu/InSite?page=kb-04-01-10#S5.5

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