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

2. 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

3. 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

4. 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

5. 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

7. 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

8. 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

9. 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

10. 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

11. First, Normal Beans

12. EPITHELIAL HYPERTROPHY

13. Collapsing FSGS in HIVAN

14. Proteinaceous Casts

15. Tubuoreticular Inclusions
HIV
SLE
IFNalpha in HCV

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

18. 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

19. 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

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