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Kidney and bone disease in HIV Dr Frank Post Clinical Senior Lecturer Kings College London Slide 2 Case 1 (October 2004) 33 yrs old lady Zimbabwe New HIV diagnosis; CD4 1 and HIV RNA 530,000 Disseminated tuberculosis HBV/HCV negative Creatinine 300; eGFR 20 mL/min; Proteinuria 5 g/24h Normal sized, echogenic kidneys HIVAN on biopsy Commenced cART current CD4 450, VL Slide 3 Black ethnicity CD4Slide 4 HIVAN in the UK (1998-2004) 16,834 patients HIVAN prevalence in Black patients: 0.93% HIVAN incidence (in patients without renal disease at BL): 0.61/1000 py Overall survivalRenal survival Clin Infect Dis 2008; 46: 1282-9 Slide 5 Natural History of HIVAN Cohort of 42 patients with HIVAN and 47 patients with renal diseases other than HIVAN Use of HAART associated with slower progression to RRT Kidney Int 66: 1145 (2004) Cohort of 36 patients with HIVAN Complete suppression of HIV replication may slow progression to RRT Nephrol Dial Transplant 2006; 21: 2809 Slide 6 Characteristics of HIVAN patients with late onset ESRF / stable renal function BaselineESRD>3 months after HIVAN diagnosis (n=20) Stable RF (n=23) eGFR (mL/min)28 (12-42)29 (17-38) Proteinuria (g/24h)5.9 (3.9-9.2)4.9 (4.0-7.1) CD4 T-cell count66 (39-140)77 (34-197) Clin Infect Dis 2008; 46: 1282-9 cART CD4>200 VL Case 4 (April 2006) 28 yrs old man Portugal HIV diagnosis 1998; CD4 54 and HIV RNA >500,000 HBV/HCV negative 1998-2002 AZT/3TC/EFV d4T/ddI/IDV/r 2002 onwards: TFV/d4T/LPV/rTFV/d4T/ATV/r 2006: Painful ribcage, lumbar spine and metatarsal joints Raised ALP (227), hypophosphatemia (0.47) Normal creatinine / eGFR 3+ glycosuria (no DM), 1+ proteinuria (PCR 14.7) Reduced fractional excretion of P (57%) Normal vitamin D and PTH Slide 20 Fanconi syndrome Prevalence: 1-2% of patients receiving Tenofovir Bone pain Phosphate wasting Osteomalacia Almost exclusively when tenofovir is co-administered with a (boosted) PI Slide 21 Tenofovir-associated renal toxicity HIV8, Glasgow 2006 100% of patients had evidence of reduced phosphate re-absorption Slide 22 284 consecutive HIV patients Median creatinine clearance 109-123 mL/min 22% of 154 on TFV 6% of 49 on cART/no TFV 12% of 81 no cART KTD in HIV infected patients AIDS 2009;23:689-96 Slide 23 Clin Infect Dis. 2009;48:e108-16 Risk factors for KTD while receiving tenofovir Role of polymorphisms in genes encoding drug transporters Curr Opin Infect Dis 2009; 22: 43-48 Slide 24 AIDS 2008;22:481-7 Effects of cART on renal function AZT/3TC/NVP or AZT/3TC/TFV Clin Inf Dis 2008;46:1271-81 Clin Inf Dis 2008;46:1271-81, AIDS 2008;22:481-7, AIDS 2009; 23: 2143-9 Slide 25 cART and CKD progression Mocroft et al. AIDS 2010 Slide 26 Proteinuria in the ALLRT cohort (n=2857) Prevalence 16% (>200 mg/d; 3% > 1 g/d) Little change in the amount of proteinuria over time Associated with: older age, HPT, DM, reduced eGFR reduced CD4, prior ART, HIV viraemia, HCV co-infection Antivir Ther 2009; 14: 543-49 Slide 27 Proteinuria as a marker of chronic kidney disease in HIV Proteinuria in 2057 HIV+ women: Prevalence (2x dipstix 1+): 32% Risk factors for proteinuria (OR): Log HIV RNA1.05* CD4