Table 6. Objectives and definitions of renal dysfunction of each study.

ADR: adverse drug reaction; CKD: chronic kidney disease; CKD-EPI: chronic kidney disease epidemiology collaboration; DAD: data collection on adverse events of anti-HIV drugs; eGFR: estimated glomerular filtration rate; FE: fractional excretion; HIV: human immunodeficiency virus; KTD: kidney tubular disease; MDRD: modification of diet in renal disease; PLWH: people living with HIV; sCr: serum creatinine; TDF: tenofovir disoproxil fumarate; TLE: TDF lamivudine efavirenz; WHO: World Health Organization

Author and year of publication	Age group of interest	Definition	Objectives
Yazie et al. 2019 [17]	≥18 years	After starting a TDF-based antiviral therapy, renal dysfunction was defined as an eGFR drop of more than 25% from baseline. In patients with HIV, eGFR was calculated using the CKD-EPI equation	To evaluate the prevalence of renal impairment, risk factors for it, and the average change in eGFR in HIV-infected patients taking TDF-based antiretroviral therapy. This study serves as a guide for the early identification of renal impairment
Agrawal et al. 2022 [18]	18–60 years	If the following conditions were satisfied, nephrotoxicity was determined: 1. An increase in serum creatinine of 0.3 mg/dL within two days, 1.5 to 1.9 times baseline within seven days, or 0.3 mg/dL but within normal limits is also a sign of significant renal damage because the usual range is between 0.5 and 1.5 mg/dL. 2. Hypouricemia as observed in Fanconi syndrome affects the proximal tubules (normal values: 2.6–6.0 mg/dL). 3. Unusual grades of +1 and +2 for the albumin-creatinine ratio in spot urine. 4. Anemia (normal hemoglobin for women is 12 and for men is 13)	The purpose of this study was to (1) Determine the frequency of nephrotoxicity brought on by tenofovir in the TLE regimen and compare it to non-tenofovir-based antiretroviral regimens using laboratory criteria. 2. To determine the time frame for the beginning of nephrotoxicity. 3. To analyze the causality of ADR using the WHO causality scale
Lee et al. 2019 [19]	More than 20 years	Greater than a 25% reduction in the initial eGFR was considered renal impairment. Using the CKD-EPI equation, eGFR was calculated	The study performed a single-center retrospective cohort to assess the prevalence and contributing variables of TDF-associated nephrotoxicity in HIV-infected patients in Korea
Agbaji et al. 2019 [20]	>18 years	Renal impairment was deemed to exist when at least one of two criteria was met. According to the Kidney Disease Outcomes Quality Initiative recommendations, stage 3 or greater renal disease is defined as eGFR less than 60 mL/minute/1.73m2 (calculated using the (MDRD) calculation). The risk, injury, failure, loss, and end-stage kidney criteria define renal injury as a rise in SCr higher than or equal to two times that of baseline or an increase in CrCl greater than 50% from baseline on one or more measurements	Study to assess the impact of prolonged TDF exposure on renal function in a cohort of HIV-1-infected Nigerians
Tan et al. 2019 [21]	>18 years	eGFR less than 90 mL/minute/1.73m2 or a reduction of more than 25% from baseline were both considered signs of TDF-related renal impairment. For the CKD-EPI, a reduction in eGFR of more than 10 mL/minute/1.73m2 from baseline was considered to indicate decreased renal function. B2 microglobulin’s normal range was less than 0.5 mg	Assessed the prevalence of renal impairment among Chinese patients who had received TDF-containing ART regimens for an extended period
Hsu et al. 2020 [22]		eGFR less than 60 mL/minute/1.73m2, more than two instances in a 90-day period apart, was considered to indicate CKD. Using the DAD CKD risk score, the baseline risk of developing CKD for each individual was calculated	A large cohort study of PLWH in the USA. Using the baseline DAD CKD risk score, determine the risk of CKD related to the use of TDF. The goal of this study was to comprehend how baseline CKD risk affected this association. Pharmacoenhancers’ effects on the discovered link between TDF and CKD were also assessed
Yilma et al. 2020 [23]	≥18 years	The participants were divided into three groups based on the change in eGFR over the previous 12 months: “decliner” if the change was >3 mL/minute/1.73m2, “stable” if the change was between -3 and 3 mL/minute/1.73m2, and “riser” if the change was >3 mL/minute/1.73m2	Focus on TDF, sought to evaluate parameters related to renal function changes throughout the first year of ART
Karoney et al. 2022 [24]	18–79 years	Any two of the following four parameters—metabolic acidosis, beta-2 microglobulinuria, and fractional excretion of phosphate greater than 20%—were considered indicators of proximal tubular renal failure. Normoglycemic glucosuria was characterized by dipstick detection of glucose in the urine despite a random blood glucose of less than 11.1 mmol/L. Less than 20 mmol/L of plasma bicarbonate was considered metabolic acidosis. Beta 2 microglobulin levels in urine that are high (more than 0.3 mg/mmol) are referred to as tubular proteinuria. Fractional excretion of phosphate (FEphos) of more than 20% in persons with normal blood phosphate levels (0.85 to 1.45 mmol/L) or more than 10% in participants with hypophosphatemia (serum phosphates of less than 0.85 mmol/L)	This cross-sectional study evaluated the overall renal function, proximal tubular renal impairment, and their predictors among patients on TDF-containing versus TDF-sparing regimens
Ng'umbi et al. 2022 [25]	>18 years	When at least two of the following criteria are present, it is renal tubular dysfunction. Phosphate wasting: FEphos levels of more than 20% in individuals with normal serum phosphate levels (2.7–4.5 mg/dL or 0.87–1.45 mmol/L) or more than 10% in patients with hypophosphatemia (serum phosphate levels of less than 2.7 mg/dL or 0.87 mmol/L) Glucosuria: urine glucose greater than 1.7 mmol/L with plasma glucose less than 10 mmol/L; uric acid wasting: FE of uric acid greater than 10% in presence of decreasing plasma uric acid level (men less than 0.20 mmol/L, women less than 0.15 mmol/L)	The purpose of the study was to identify the prevalence and risk factors for renal tubular dysfunction in Ugandan HIV-positive individuals taking TDF-containing regimens
Nishijima et al. 2018 [26]	20 years and above	The presence of two or more abnormalities in any of the five tubular markers—beta 2 microglobulinuria, fractional excretion of phosphate, fractional excretion of uric acid, N-acetyl-b-D-glucosaminidase, or nondiabetic glycosuria—was predefined as KTD. The Japanese equation created by the Japanese Society of Nephrology was used to determine eGFR based on standardized serum creatinine, sex, and age	This research was done to show that TDF increases the risk of renal tubular dysfunction and to determine if kidney tubular dysfunction (KTD) endures after TDF is stopped