Chronic kidney disease in an inner London HIV Cohort Annual Conference of the British Association of Sexual Health and HIV April 6th-8th,Bournemouth, UK Chronic kidney disease in an inner London HIV Cohort St George’s NHS Trust South West London HIV & GUM Clinical Services Network Nicola Jonesa, Aseel Hegazib, Mark Pakianathanb, Phillip Hay a aSt George’s University of London, Cranmer Terrace, London SW17 0RE bCourtyard Clinic, St George’s Hospital, Blackshaw Rd, London SW17 0QT Background Estimated Glomerular Filtration Rate (eGFR) and the presence of proteinuria are both associated with progression of chronic kidney disease (CKD), the development of cardiovascular disease and subsequent mortality. CKD in HIV infected patients is associated with age, advanced disease stage, diabetes, hypertension, vascular disease and the use of medication including antiretrovirals such as tenofovir and atazanavir2-4. HIV-associated nephropathy (HIVAN) is almost exclusively seen in patients of black ethnicity and black patients are at increased risk of progression to end stage renal failure and requiring dialysis5. Creatinine based methods for estimating Glomerular Filltration Rate (GFR) are widely used but have not been validated in HIV-infected populations. The laboratory routinely reports eGFR based on the Modification of Diet in Renal Disease (MDRD) equation, shown below: The Cockroft-Gault (C-G) method of estimation is the standard method used in determining the need to dose adjust renally excreted drugs and may be more accurate than MDRD for this purpose 1. Dose modification of commonly used antiretrovirals such as tenofovir and lamivudine is recommended based on calculated eGFR based on the C-G equation, however this requires a knowledge of patients’ weight and is not routinely calculated in clinical practice. CG is calculated based on the following equation: Proteinuria - Urine Protein/Creatinine ratio (UPCR) was available for 871/1121 patients, shown below in table 3. Dose Adjustment of Antiretroviral Therapy - Within the low MDRD GFR group, 2 of the 10 patients still on tenofovir had not been appropriately dose adjusted and 4 of the 16 patients still on lamivudine had not been appropriately adjusted according to their renal function based on CG GFR. Patients with Stage 3 or Greater CKD - 35 patients had a MDRD eGFR of less than 60.0 mL/min/1.73 m2. 9 patients in this group (26%) were on dialysis and 4 were awaiting renal transplantation. 31.4% (11/35) of patients in this cohort had a UPCR ≥ 45mg/mmol (macroalbuminuria) and 28.6% (10/35) were found to have a trace of protein. The main renal diagnosis of patients in this group is shown in table 4. 54.3% (19/35) were known to have hypertension, 22.9% (8/35) had diabetes, 20% (7/35) were using NSAIDs and 37.1% (13/35) were prescribed ACE inhibitors. 68.6% (24/35) had been treated with tenofovir and in 12 of the 35 patients renal disease had been attributed to tenofovir. 40% had been exposed to atazanavir. Aims To estimate the renal function of a cohort of HIV infected adults attending the Courtyard Clinic using the C-G formula for estimating eGFR in comparison to the MDRD equation. To describe identified causes of renal disease in patients with an MDRD GFR of < 60 mL/min/1.73 m2. To describe the prevalence and extent of proteinuria within this cohort To determine if appropriate dose adjustment of antiretroviral medication had been made in patients when this was indicated by eGFR. Methods Patients attending the HIV clinic between 1/1/9 and 31/12/10 were identified and data extracted from the HIV clinical database. Medical records of patients with an MDRD GFR <60.0 mL/min/1.73 m2 (indicating renal function of moderate to end-stage renal failure) were reviewed to identify risk factors for renal impairment, including NSAIDs, tenofovir and atazanavir exposure, BMI, hypertension and other relevant co morbidities as well as renal diagnoses and management.  Discussion a More patients were identified as having CKD using CG than MDRD. Whilst CG may underestimate eGFR in black patients we unexpectedly found a greater discrepancy between the two equations in patients of non-black ethnicity. This difference may have been attenuated to a large extent by the high prevalence of obesity in our cohort which is known to lead to overestimation of CG eGFR. The relatively high prevalence of proteinuria seen requires further evaluation and is similar to that seen in other cohorts. More widespread use of ACE inhibitors may be warranted in HIV-infected populations to delay progression of CKD. Recommendations on dose modification of most renally excreted drugs in the UK is based on CG rather than MDRD eGFR and failure to modify the dose of antiretroviral drugs in some of our patients may have been due to the use of the MDRD eGFR as a substitute for CG eGFR. The standard definition of CKD requires two creatinine levels from samples taken on two separate occasions 6 months apart and undoubtedly the use of serial creatinine values for each patient would have strengthened our study. Our study was retrospective and incomplete drug histories and other missing data may have had an impact on our results. Results Study Population – eGFR was calculated for 1121 patients using CG and MDRD equations using the most recently measured creatinine value and was stratified by CKD stage. Patients were 57% male with a median age of 43.6 yrs (IQR 37.8 – 49.8 yrs). 60.3% were of black ethnicity and 33.6% were white. 73.0% of patients (818/1121) were prescribed tenofovir, 21.0% atazanavir and 14.5% both drugs. 24.2% (236/1121) of the cohort were classified by BMI as obese and 1.7% (17/1121) were considered wasted with a BMI of <18.5. 145 patients had no value recorded. BMI distribution between the sexes are shown in table 1. eGFR - The prevalence of CKD stage 3 or above was 9% using CG to estimate eGFR but only 1.1% using MDRD. This difference was greater in non-black patients (0.7% vs. 10.8%) than in black patients (1.3% vs. 7.7%), and less marked in those with a BMI ≥25 (1% vs. 4.7%). A comparison is shown in table 2. Conclusions We found a higher prevalence of CKD using CG to measure eGFR than MDRD. Further research is needed to validate simple methods for the early detection of CKD in HIV infected populations which may allow for intervention to halt disease progression. Acknowledgements Many thanks to Barbara Edgeley, Helen Webb and the HIV nursing team, staff and patients at the Courtyard Clinic, St. George’s Hospital. References 1. Roblin I, De Sobarnitsky S, Basselin C, Vial F, Bard E, et al.Estimated glomerular filtration rate for drug dose adjustment: Cockcroft and Gault or abbreviated MDRD equation? Clin Biochem. 2009;42(1-2):111-3. 2. Post F. A, Holt S. G. Recent developments in HIV and the kidney. CurrOpin Infect Dis. 2009;22(1):43-8. 3. Naicker S, Han T. M, Fabian J. HIV/AIDS—Dominant player in chronic kidney disease. Ethn Dis. 2006;16:S2-56-60. 4. Rodriguez-Nόvoa S, Alvarez E, Labarga P, Soriano V. Renal toxicity associated with tenofovir use. Expert Opin Drug Saf. 2010;9(4):545-59. 5. Hsu C. Y, Iribarren C, McCulloch C. E, Darbinian J, Go A. S. Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med. 2009;169(4):342-50.