Assessment of renal function in routine care of people living with HIV on ART in a resource-limited setting in urban Zambia

<div><p>Introduction</p><p>Data on renal impairment in sub-Saharan Africa (SSA) remains scarce, determination of renal function is not part of routine assessments. We evaluated renal function and blood pressure in a cohort of people living with HIV (PLWH) on antiretroviral treatment (ART) in the Renal Care Zambia project (ReCaZa).</p><p>Methods</p><p>Using routine data from an HIV outpatient clinic from 2011–2013, we retrospectively estimated the glomerular filtration rate (eGFR, CKD-Epi formula) of PLWH on ART in Lusaka, Zambia. Data were included if adults had had at least one serum creatinine recorded and had been on ART for a minimum of three months. We investigated the differences in eGFR between ART subgroups with and without tenofovir disproxil fumarate (TDF), and applied multivariable linear models to associate ART and eGFR, adjusted for eGFR before ART initiation.</p><p>Results and discussion</p><p>Among 1118 PLWH (63,3% female, mean age 41.8 years, 83% ever on TDF; median duration 1461 [range 98 to 4342] days) on ART, 28.3% had an eGFR <90 ml/min, and 5.5% <60 ml/min at their last measurement. Information on other conditions associated with renal impairment was not systematically documented. Fourteen per cent of the PLWH who later switched to TDF-free ART had an initial eGFR lower 60ml/min. Nineteen percent had first-time hypertensive readings at their last visit. The multivariable models suggest that physicians acted according to guidelines and replaced TDF-containing ART if patients developed moderate/severe renal impairment.</p><p>Conclusions</p><p>Assessment of renal function in SSA remains a challenge. The vast majority of PLWH benefit from long-term ART, including improved renal function. However, approximately 5% of PLWH on ART may have clinically relevant decreased eGFR, and 27% hypertension. While a routine renal assessment might not be feasible, strategies to identify patients at risk are warranted. Targeted monitoring prior and during ART is recommended, however, should not delay ART access.</p></div

HIV and renal impairment related variables at two specific points in time of HIV patients on ART at Chreso Ministries in Lusaka, Zambia, between 2011–2013 and KDGIO eGFR category classification.

<p>HIV and renal impairment related variables at two specific points in time of HIV patients on ART at Chreso Ministries in Lusaka, Zambia, between 2011–2013 and KDGIO eGFR category classification.</p

Multivariate linear regression models: i) adjusted for initial eGFR, age, sex, time of HIV duration, plus three ART categories; ii) adjusted for ART categories at last measurement (sensitivity analysis); iii) adjusted for specific ART regimen at last measurement (sensitivity analysis).

<p>Multivariate linear regression models: i) adjusted for initial eGFR, age, sex, time of HIV duration, plus three ART categories; ii) adjusted for ART categories at last measurement (sensitivity analysis); iii) adjusted for specific ART regimen at last measurement (sensitivity analysis).</p

Differences at last measurement between HIV patients who had never received TDF-containing ART(ART_{TDF free}), those who continuously took a TDF-containing ART (ART_TDF), and those who switched to TDF free (ART_switched) at Chreso Ministries in Lusaka, Zambia 2011–2013.

<p>Differences at last measurement between HIV patients who had never received TDF-containing ART(ART_{TDF free}), those who continuously took a TDF-containing ART (ART_TDF), and those who switched to TDF free (ART_switched) at Chreso Ministries in Lusaka, Zambia 2011–2013.</p

Study population flowchart.

<p>Study population flowchart.</p

ARTs regimen as documented at time of last creatinine measurement.

<p>A = Stavudine (d4T), 3TC, Nevirapine (NVP); B = AZT, 3TC, Efavirenz (EFV); C = Abacavir (ABC), 3TC, EFV; D = TDF, Emtricitabine (FTC), EFV; E = ABC, Lopinavir (LPV), Ritonavir (rtv); F = TDF, FTC, LPV/rtv; G = AZT, 3TC, NVP; H = TDF, FTC, NVP; I = ABC, 3TC, NVP; J = not classifiable/other combinations.</p

Initial eGFR categories and those at time of last creatinine measurement, separated by changes in ART regimen (N = 565).

<p>Initial eGFR categories and those at time of last creatinine measurement, separated by changes in ART regimen (N = 565).</p

Effects of Increased Von Willebrand Factor Levels on Primary Hemostasis in Thrombocytopenic Patients with Liver Cirrhosis

<div><p>In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180±62 s with Col-Epi and 160±70 s with Col-ADP. Multivariate analysis revealed that hematocrit (<i>P</i> = 0.027) and vWF-antigen levels (<i>P</i> = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥150/nL and hematocrit ≥27.0%, pathological PFA-100 results were found. In thrombocytopenic (<150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3±235.9% vs. 338.7±151.6%, <i>P</i> = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.</p></div

Characteristics of patients with liver cirrhosis.

<p>Description of baseline parameters such as age, sex, and etiology of patients with liver cirrhosis and labMELD-score; grouped by Child-Turcotte-Pugh score.</p>a<p>Including primary sclerosing cholangitis and biliary atresia.</p>b<p>Including Wilson disease and polycystic liver disease.</p><p>Characteristics of patients with liver cirrhosis.</p

Results for univariate analysis of predictors of a pathological PFA-100 test result.

<p>Univariate analysis of the following variables was performed to identify predictors of a pathological PFA-100 test results in the whole study cohort and in thrombocytopenic cirrhotic patients. Multivariate analysis was then performed with variables showing a <i>P</i>-value ≤0.1 in univariate analysis.</p><p>Results for univariate analysis of predictors of a pathological PFA-100 test result.</p