ART Use and Kidney Function: Clinical Practice Implications
ART Use and Kidney Function: Clinical Practice Implications
Many of the current and forthcoming antiretrovirals have the potential to affect kidney function. Rilpivirine, DTG, COBI, RTV, and possibly RTG, affect tubular creatinine transport without apparent renal toxicity. Lopinavir/ritonavir has been associated with eGFR decline, although evidence for direct adverse effects on the kidney is currently lacking. Tenofovir-DF and ATV clearly have nephrotoxic potential, although overt renal toxicity is uncommon. The challenge in clinical practice is to distinguish the benign mild to moderate aberrations in renal biomarkers from clinically significant toxicity.
International guidelines, based on expert opinion, recommend that renal function (eGFR and urinalysis) is assessed at the time of HIV diagnosis, prior to initiating cART, and during clinical follow up. It seems prudent to adhere to this recommendation and ensure that renal function is reassessed after 4 weeks in those who receive RPV, DTG, COBI, RTV and RTG to establish the new 'eGFR setpoint' as a reference to compare subsequent measurements. eGFR declines of 10–20% can be anticipated with these drugs and should not immediately raise concern if nonprogressive and seen in isolation. Patients with substantial eGFR reduction at 4 weeks should have this rechecked a month later to ensure that no further decline has occurred. Where these drugs are coadministered with TDF, urinalysis and measurement of urine protein: creatinine ratio should be performed to rule out (worsening) proteinuria, haematuria or normoglycaemic glycosuria as manifestations of renal tubular disease. Tubular function can be further evaluated by measurement of low molecular weight proteins and calculation of the fractional excretion of phosphorus if (fasting) hypophosphataemia is present. In most patients stable on cART with undetectable HIV RNA levels and preserved renal function, annual assessment of renal function is likely to suffice, although the optimal frequency of renal monitoring has not been studied.
In patients with normal renal function, progression to advanced CKD (eGFR <30 ml/min per 1.73 m) is very uncommon and drugs such as TDF and ATV have an excellent safety profile in these individuals. By contrast, patients with impaired renal function are at a greater risk of renal disease progression and should be monitored more carefully. The risk of eGFR decline and overt renal toxicity is increased with TDF and ATV/RTV, and these drugs are best avoided in patients with CKD and impaired renal function.
Substantial fluctuations between serum creatinine measurements are observed in clinical practice, and treatment decisions should not be based on single GFR estimates. Previous eGFR measurements, urinalysis, clinical status, comorbidities and comedications are important in establishing the probable cause of renal dysfunction. Rapidly progressive decline in eGFR and significant proteinuria (>500–1000 mg/24 h) are distinctly uncommon and should lead to further investigations to establish the exact cause. This includes a renal ultrasound and not infrequently a renal biopsy. Conversely, more gradual eGFR decline and/or mild–moderate proteinuria should focus on a review and management of risk factors, including hypertension, diabetes mellitus, exposure to nephrotoxic medications and urological disease, and liaison with a nephrologist should be considered.
Antiretrovirals and the Kidney: Opinion-Based Recommendations for Clinical Practice
Many of the current and forthcoming antiretrovirals have the potential to affect kidney function. Rilpivirine, DTG, COBI, RTV, and possibly RTG, affect tubular creatinine transport without apparent renal toxicity. Lopinavir/ritonavir has been associated with eGFR decline, although evidence for direct adverse effects on the kidney is currently lacking. Tenofovir-DF and ATV clearly have nephrotoxic potential, although overt renal toxicity is uncommon. The challenge in clinical practice is to distinguish the benign mild to moderate aberrations in renal biomarkers from clinically significant toxicity.
International guidelines, based on expert opinion, recommend that renal function (eGFR and urinalysis) is assessed at the time of HIV diagnosis, prior to initiating cART, and during clinical follow up. It seems prudent to adhere to this recommendation and ensure that renal function is reassessed after 4 weeks in those who receive RPV, DTG, COBI, RTV and RTG to establish the new 'eGFR setpoint' as a reference to compare subsequent measurements. eGFR declines of 10–20% can be anticipated with these drugs and should not immediately raise concern if nonprogressive and seen in isolation. Patients with substantial eGFR reduction at 4 weeks should have this rechecked a month later to ensure that no further decline has occurred. Where these drugs are coadministered with TDF, urinalysis and measurement of urine protein: creatinine ratio should be performed to rule out (worsening) proteinuria, haematuria or normoglycaemic glycosuria as manifestations of renal tubular disease. Tubular function can be further evaluated by measurement of low molecular weight proteins and calculation of the fractional excretion of phosphorus if (fasting) hypophosphataemia is present. In most patients stable on cART with undetectable HIV RNA levels and preserved renal function, annual assessment of renal function is likely to suffice, although the optimal frequency of renal monitoring has not been studied.
In patients with normal renal function, progression to advanced CKD (eGFR <30 ml/min per 1.73 m) is very uncommon and drugs such as TDF and ATV have an excellent safety profile in these individuals. By contrast, patients with impaired renal function are at a greater risk of renal disease progression and should be monitored more carefully. The risk of eGFR decline and overt renal toxicity is increased with TDF and ATV/RTV, and these drugs are best avoided in patients with CKD and impaired renal function.
Substantial fluctuations between serum creatinine measurements are observed in clinical practice, and treatment decisions should not be based on single GFR estimates. Previous eGFR measurements, urinalysis, clinical status, comorbidities and comedications are important in establishing the probable cause of renal dysfunction. Rapidly progressive decline in eGFR and significant proteinuria (>500–1000 mg/24 h) are distinctly uncommon and should lead to further investigations to establish the exact cause. This includes a renal ultrasound and not infrequently a renal biopsy. Conversely, more gradual eGFR decline and/or mild–moderate proteinuria should focus on a review and management of risk factors, including hypertension, diabetes mellitus, exposure to nephrotoxic medications and urological disease, and liaison with a nephrologist should be considered.
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