Renal Manifestations of HIV/AIDS Ryan Sanford 7/17/09

Medications – FTD! Ayclovir – ATN, crystalluria, obstructive nephropathy Adefovir – Fanconi’s syndrome AMGs – ATN, RTA, Bartter’s Syndrome, Fanconi’s AMB – ATN, RTA, K and Mg Cidofovir – proximal tubule damage, HCO3- wasting Foscarnet – electrolytes, nephrogenic DI Indinavir – crystalluria and obstructive nephropathy NSAIDS – ATN, AIN Pentamidine – ATN, K and Ca Rifampin – AIN Sulfadiazine – Cyrstalluria, obstructive nephropathy, AIN

Aminoglycosides PCT: includes . . . receptor mediated endocytosis higher affinity for mitocondrial ribosomes Mitochondrial dysfunction  loss of ATP Loss of basolateral Na/K ATPase Generation of proximal RTA or Fanconi syndrome

Aminoglycosides Thick ascending limb: Calcium Sensing Receptor [CaSR] on basolateral surface senses elevated Ca++, and leads to calciuria by inhibiting NKCC transporters and Na/K ATPase Bartters like syndrome [hypoMg, hypoCa, hypoK, metabolic alkalosis] in AMG use 2/2 activation of CaSR

Trimethoprim Collecting Duct GFR ≠ CrCl 2/2 some Cr secretion Inhibits ENaC [aldo] Loss in Na influx No K efflux to lumen 2/2 loss of lumen negative charge Hyperkalemia GFR ≠ CrCl 2/2 some Cr secretion TMP can inhibit this secretion, increasing SCr Not a reflection of decreased GFR

AKI Similar causes and approach to non HIV population Prerenal: increased with diarrhea, fever, poor PO Instrinsic: nephrotoxins, changed hemodynamics 50% AKI 2/2 ischemic injury 25% AKI 2/2 nephrotoxins Postrenal: crystal induced obstruciton Indinavir, acyclovir, sulfadiazine Thrombotic Microangiopathies [TMAs] HUS/TTP increasingly recognizied in HIV

CKD HIV Associated Nephropathy (HIVAN) Also Most common cause of CKD in HIV patients #3 cause of ESRD in African Americans between 20 and 64y Renal Bx imperative! – 40% of suspected HIVAN will be a different diagnosis Also Membranoproliferative GN Minimal change disease Membranous glomerulopathy IgA nephropathy

HIVAN Presentation Largely restricted to African Americans – 90% Other 10% - mixed heritage or Hispanics S/Sx Proteinuria, then azotemia Normotensive Large, echogenic kidneys on renal u/s Typically w/ CD4 < 200, but also seen at seroconversion Progress to ESRD in weeks to months

HIVAN Pathology FSGS and microcystic distortion of tubulointerstitium FSGS often of collapsing variant [but not pathognomonic] Microcysts filled with proteinaceous casts Proliferation of epithelial cells Proliferation of podocytes Some interstitial infiltration of immune cells Interstitial fibrosis EM: tubuloreticular inclusions

First, Normal Beans

EPITHELIAL HYPERTROPHY

Collapsing FSGS in HIVAN

Proteinaceous Casts

Tubuoreticular Inclusions HIV SLE IFNalpha in HCV

HIVAN Pathogenesis A direct role of the virus Renal epithelium able to support viral reproduction Renal epithelium an HIV reservoir

Management - ESRD CKD and HIV Transplant candidates: Undetectable viral burden Stable HAART regimen No evidence of OI or neoplasm CD4 > 200 ESRD: standard precautions and CKD therapy

Management - HIVAN Most evidence from poorly designed studies/observations ACEi: esp if SCr <2 mg/dL Corticosteroids: potential benefit; Increased OIs? Cyclosporine: has been used Progression to ESRD slowed by HAART

Reference Primer on Kidney Disease, 5th Edition UNC Nephropathology Lab, http://www.uncnephropathology.org/ Atlas of Diseases of the Kidney; http://www.kidneyatlas.org/ Winston et al. Nephropathy and Establishment of a Renal Reservoir of HIV Type 1 During Primary Infection. NEJM 344; 26:1979-1985 Zietse R et al. Fluid, electrolyte, and acid-base disorders associated with antibiotic therapy. Nature Rev Nephrol. 5, 193-202 (2009)