Table 1 Evidence of renal dysfunction in the included studies

Brennan et al. 2011 [27]

Creatinine clearance using Cockcroft-Gault (CG) equation.

Nephrotoxicity defined as any decline in kidney function from baseline (acute or chronic) that is secondary to a toxin (including drugs) documented within 48 months of initiating tenofovir (TDF).

Normal renal function (> 90 ml/min), mild renal dysfunction (60–89 ml/min) and moderate renal dysfunction (30–59 ml/min)

The risk of nephrotoxicity and death by 48 months increased with decreasing renal function at initiation of TDF. Patients switched onto TDF had a higher risk of nephrotoxicity and death compared to ART naïve patients.

Median time to nephrotoxicity after TDF initiation is 3.6 months confirming the importance of the month 3 creatinine clearance.

Fabian et al. 2009 [16]

Urine dipstick for proteinuria and microalbuminuria

Microalbuminuria: microalbumin-to-creatinine ratio 3.4–33.9 mg/mmol independent of sex;

overt proteinuria: protein-to-creatinine ratio of 0.03–0.3 g/mmol;

nephritic range proteinuria: protein-to-creatinine ratio > 0.3 g/mmol.

18.5% had microalbuminuria, 6.4% had overt proteinuria and 2.4% had nephrotic range proteinuria.

Fabian et al. 2013 [15]

Urine dipstick for proteinuria.

Estimated glomerular filtration rate (eGFR) using both CG and 4 variable Modification of Diet in Renal Disease (MDRD) formulae.

Renal biopsy

Persistent microalbuminuria: microalbumin-to-creatinine ratio of 3.4–33.9 mg/mmol;

Persistent overt proteinuria: protein-to-creatinine ratio of 34 mg/mmol-0.3 g/mmol;

Nephrotic proteinuria: protein-to-creatinine ratio > 0.3 g/mmol.

68% had microalbuminuria, 23% had overt proteinuria and 9% had nephrotic proteinuria.

There was an improvement in eGFR on antiretroviral treatment (ART). There was partial or complete remission of proteinuria in response to treatment. Despite the rapid clinical response to ART, there was relative lack of histological resolution.

Franey et al. 2009 [33]

Urine dipstick for proteinuria.

eGFR using the four variable MDRD equation.

Urine dipstick for proteinuria

Severe renal impairment: eGFR < 30 mls/min/1.73m²;

Moderate renal impairment: eGFR 30–60 mls/min/1.73²;

mild renal impairment: eGFR 60–90 mls/min/1.73².

Proteinuria ≥ 1+ protein on dipstick.

Renal dysfunction defined as either reduced eGFR and/or proteinuria/haematuria.

Severe renal impairment was uncommon while moderate and mild renal impairment were more common. Mild and moderate renal impairment improve on ART. Urine analysis may not be sufficiently sensitive to be used as a single screening test for renal disease at baseline.

Kamkuemah et al. 2015 [32]

eGFR calculated using CG equation

Severe renal function reduction was defined as eGFR < 30 ml/min/1.73 m², moderate reduction as eGFR of 30–59 ml/min/1.73 m² and mild reduction as an eGFR of 60–89 ml/min/1.73 m².

79% had normal renal function at baseline, 19% had mildly reduced renal function and 2% had moderate renal impairment at baseline. Overall renal function improved over the first year after starting TDF-containing ART regimens.

Madala et al. 2014 [34]

Urine dipstick for proteinuria.

eGFR calculated using the MDRD equation for ≥ 18 years and the Schwartz equation for < 18 years old.

Chronic kidney disease (CKD) defined by eGFR < 60 ml/min/1.73m² and/or proteinuria and/or abnormal renal ultrasound, persistent for ≥ 3 months.

eGFR was < 30 ml/min/1.73m² in 50.6% of patients as this was a CKD clinic. Main risk factors for CKD were diabetes, hypertension and HIV.

Vachiat et al. 2013 [29]

Urine for proteinuria either dipstick or spot urine protein creatinine ratio.

Serum creatinine levels.

Acute kidney injury (AKI) defined as an improvement in admission serum creatinine of > 50%. They were further subdivided using the rifle criteria: risk—serum creatinine < 194 μmol/L; injury—serum creatinine 195 to 291 μmol/L; and failure—serum creatinine > 291 μmol/L.

Majority had AKI 56%, followed by CKD 23% and 21% had acute on chronic kidney disease. Proteinuria did not predict recovery or death in HIV-infected patients with AKI. AKI was common in HIV-infected patients and occurred at a younger age than HIV negative patients.

Wearne et al. 2012 [31]

Renal biopsy

Serum creatinine

Urine protein creatinine ratio

HIV-associated nephropathy (HIVAN) defined as a constellation of glomerular, interstitial and tubular abnormalities, and there must be epithelial cell hyperplasia if only tubular or interstitial disease was present.

For patients with HIVAN, there was an improvement in proteinuria and stabilisation of renal function after commencing ART. Renal biopsy is essential to diagnose renal disease in HIV-infected patients.

Wensink et al. 2015 [35]

Urine for albuminuria

eGFR calculated using MDRD and CKD epidemiology collaboration formula

Moderately increased albuminuria: albumin creatinine ratio 30 to 299 mg/g;

Severely increased albuminuria: albumin creatinine ratio > 300 mg/g.

Albuminuria occurred in 20% of patients while only 2% had eGFR < 60 ml/min/1.73m². Higher eGFR was significantly linked to lower prevalence of albuminuria. Albuminuria was linked to higher frequency of diabetes, hypertension, high total cholesterol and decreased eGFR.