Clinical Case Scenario

A 56-year-old man with a 5-year history of HIV-1, previously managed with elvitegravir, emtricitabine, and tenofovir disoproxil fumarate (TDF) but lost to follow-up, presented to the ICU with acute hypoxic respiratory failure. He reported a week of fever, dry cough, and musculoskeletal pain, treated with NSAIDs. In the emergency department, he was hypertensive (200/111 mmHg), tachypneic (RR 26), and hypoxic, requiring 15 L/min oxygen via non-rebreather mask to maintain SpO2 >94%. Examination revealed bilateral pitting pedal edema to the knees, oliguria, and volume overload. He was stabilized and admitted to the ICU.

Labs: Creatinine 4.7 mg/dL (baseline 2.5 mg/dL), RBC 3-5/HPF, glucosuria (+), proteinuria (3+), spot urine protein/creatinine ratio 5.2 mg/mg (ref <0.10 mg/mgCr), albumin 2 g/dL, total protein 6.5 g/dL, CPK 200, Ultrasound KUB: enlarged kidneys with increased echogenicity, pH 7.29, Na 148, K 3.1, CD4/CD8 ratio 0.11, CD4 cells 86/μL, HIV viral load 119,000 copies/mL.

A renal biopsy, performed due to rapidly declining renal function and nephrotic-range proteinuria, revealed collapsing focal segmental glomerulosclerosis (FSGS), marked interstitial inflammation, dilated cystic tubules, and tubular epithelial inclusion bodies.

Continuous renal replacement therapy (CRRT) was initiated, and NSAIDs were discontinued.

Wrong Answer: The presence of glucosuria in the urine analysis, hypokalemia and hypophosphatemia indicate a possibility of proximal RTA from tenofovir ; However the more concerning issue is the hypertension and nephrotic range proteinuria .While tenofovir causes a proximal acute tubular necrosis,nephrotic range proteinuria is more indicative of a glomerular pathology. . The mainstay of therapy for HIVAN is initiating / optimizing ART as it can slow or even reverse disease progression which is not included in this option

Wrong Answer:Plasma exchange would be reserved for HIV associated -microangiopathy; However, the vignette above does not describe a thrombocytopenia or hemolytic anaemia to corroborate with TMA

Right Answer: This patient presents with advanced HIV disease, acute on chronic kidney injury, and biopsy-proven collapsing focal segmental glomerulosclerosis (FSGS)—a pattern strongly associated with HIV-associated nephropathy (HIVAN). There are a multitude of causes of AKI in HIV patients including but not limited to Pre-renal AKI , drug/ infection induced ATN, Interstitial nephritis, nephrolithiasis, immune complex disease, TMA ,etc. However, the acute onset of symptoms , nephrotic range proteinuria, suggest an acute glomerular pathology. The histopathology of collapsing Focal Segmental Glomerulosclerosis is classical of HIVAN. HIVAN is typically observed in patients who are not already receiving ART but the crucial detail in this patient is the fact that he was lost to follow up and his blood work up showed significant HIV viral load. Medication non -adherence, resistance to ART and genetic predisposition are other situations that put HIVAN into the list of differentials. Direct viral injury of the glomeruli and tubules is Patho gnomic of HIVAN. Hence optimizing the current regimen of ART by addressing non-adherence and resistance is crucial. Tenofovir nephrotoxicity is a well recognised entity and is strongly co-related with Fanconi syndrome , AKI and progression of CKD. Hence stopping tenofovir and switching to a renal safe ART regimen is a logical next step. Introduction of ACE inhibitors for proteinuria can be done once the renal function improves

Clinical Pearls

● HIV related kidney disease is multifactorial and can occur from the infection itself apart from the immune mediated responses, drug induced injury , opportunistic infections, pre and post renal causes and background co-morbid conditions
● HIVAN is the classic pattern of renal disease precipitated by direct viral injury to glomerular and tubular epithelial cells and typically presents with a collapsing focal segmental glomerilar sclerosis
● Although the incidence of HIVAN following introduction of ART is decreasing, it is an important cause of AKI and CKD in patients of HIVAN with non adherence, resistance to ART , genetic predisposition and in those patients not initiated on ART
● Initiation of a reno-safe regimen of ARTis the most definitive management of HIVAN along with avoidance of other nephrotoxic insults and RRT. Although there is limited evidence for corticosteroids for rapidly progressing HIVAN , its utility is limited to out-patient settings in select patients.

Wrong Answer: In HIVAN ,the role of steroids is nuanced and can be done only in select biopsy proven out-patient cases with collapsing glomerular disease who are rapidly progressing despite ART. In critically ill immunosuppressed patient with high viral loads and low CD4 counts the risk outweighs the benefits and hence steroids are not recommended .The therapy should focus on controlling viral replication and supportive management with RRT