Evolution of glomerular filtration rates and neutrophil gelatinase-associated lipocalin during treatment with direct acting antivirals.

Background/Aims: Correct renal function evaluation is based on estimated glomerular filtration rates (eGFR) and complementary renal damage biomarkers, such as neutrophil gelatinase associated lipocalin (NGAL). The aim of this study was to evaluate eGFR and NGAL modifications and renal impairment during treatment with a direct acting antiviral (DAA) for chronic hepatitis C virus (HCV) infection. METHODS: A retrospective cohort study evaluated eGFR modification during treatment with DAA. Subgroup analysis on serum NGAL was conducted in those receiving sofosbuvir/ledipasvir, with complete follow-up until week 12 after the end of treatment (FU-12). RESULTS: In the 102 enrolled patients, eGFR reduction was observed (from 86.22 mL/min at baseline to 84.43 mL/min at FU-12, P=0.049). Mean NGAL increased in 18 patients (from 121.89 ng/mL at baseline to 204.13 ng/mL at FU-12, P=0.014). At FU-12, 38.8% (7/18) of patients had a plasmatic NGAL value higher than the normal range (36-203 ng/mL) compared with 11.1% (2/18) at baseline (χ 2 =3,704; P=0.054). In contrast, eGFR did not change significantly over the follow-up in this subgroup. Conclusions: In conclusion, compared to a negligible eGFR decline observed in the entire cohort analyzed, a significant NGAL increase was observed after HCV treatment with DAA in a small subgroup. This could reflect tubular damage during DAA treatment rather than glomerular injury.

How to improve duration and efficiency of the antiproteinuric response to Ramipril: RamiPROT-a prospective cohort study.

BACKGROUND: The antiproteinuric pharmacokinetics of Ramipril in response to different doses and modalities of administration has been poorly investigated so far. STUDY DESIGN: Prospective, open-label and not placebo controlled study. SETTING AND PARTICIPANTS: 40 Caucasian adult patients having GFR ≥ 50 mL/min, proteinuria 1-3 g/day; SBP/DBP ≤ 150/90 mmHg were recruited between June 2014 and November 2014. FACTOR AND OUTCOME: Impact on 24 h proteinuria and fractioned proteinuria of Ramipril given at different dosages (2.5 mg/day or Ramipril 5 mg/day or Ramipril 10 mg/day) and with different daily administration modalities (single or two divided doses) for cycles of 10 days. MEASUREMENTS: At the end of each cycle, 24 h and fractioned proteinuria on three timed urinary collections (morning, afternoon and night) were measured. RESULTS: Compared to baseline, Ramipril significantly reduced 24 h proteinuria at each dose and modality of administration. In particular, the greatest effects were evident with the higher and divided dose of the drug. The analysis of the fractioned proteinuria showed that the greatest reduction was obtained in the night urinary collection by administering Ramipril 10 mg/day in two divided doses. LIMITATIONS: Small sample size. CONCLUSIONS: Ramipril reduces proteinuria at any of the tested doses. Although the using of high and divided doses seems to maximize the antiproteinuric effect of the drug, possibly due to a better pharmacological coverage of the nocturnal period.

Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

AIM: To evaluate neutrophil gelatinase associated lipocalin (NGAL) in patients infected by hepatitis C virus (HCV) before and during treatment with directly acting antivirals (DAAs). METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate (eGFR). Then, NGAL and eGFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for non-parametric data. Differences in dichotomous variables were evaluated through χ (2) test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four (FIB-4), AST to platelet ratio index (APRI), and eGFR]. RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with eGFR < 60 mL/min vs patients with eGFR ≥ 90 mL/min. Differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/dL were compared with those of NGAL ≤ 118.11 ng/dL, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis (P > 0.05). Linear correlation was found between NGAL and both age (P = 0.0475) and eGFR (P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for eGFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline (P = 0.0239). CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

[Is it feasible to improve the duration and the efficiency of Ramipril anti-proteinuric response?]. / È possibile migliorare la durata e l'efficacia della risposta anti-proteinurica di Ramipril?

BACKGROUND: Ramipril administered once daily is characterized by an attenuation of its pharmacological activity in the following 24 hours, whose effects on antiproteinuric activity have not yet been investigated. METHODS: The antiproteinuric efficacy of Ramipril has been evaluated in a cross-over study in 20 patients with renal disease, proteinuria and hypertension (GFR50 mL / min, proteinuria <3 g / day; SBP/DBP 150/90 mmHg). Proteinuria was measured over 24 hours on three consecutive urine collections (morning, afternoon and night) in the absence of antiproteinuric drugs and after ten days of treatment with single morning administration of Ramipril 2.5 mg or Ramipril 10 mg. RESULTS: At baseline: mean proteinuria was not significantlychanged over the course of the three urinary collections (88 7.2 mg/h in the morning of 80 10.5 mg/h in the afternoon and 81 10.1 mg/hr during the night). After Ramipril 2.5 mg/day: slight reduction in mean proteinuria, with no significant differences between collections (80 11 mg/h in the morning, 69 7.4 mg/h in the afternoon and 75 9.1 mg/h during the night). After Ramipril 10 mg/day: afternoon and night values of proteinuria were significantly reduced compared to baseline; noctural proteinuria was significantly lower than morning value (51 7.5 mg/h vs. 81 10 mg/h, p <0.05). CONCLUSION: The antiproteinuric effectiveness of Ramipril tends to decrease significantly over the 24hours after a single daily administration. An increase and/or division of Ramipril dose might help to stabilize and to maximizeits antiproteinuric effectiveness.