Risk Factors For Renal Impairment Research Articles

Assessment of renal safety of tenofovir disoproxil fumarate in people living with HIV in Tunisia

Background: Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor (NRTI). TDF is generally well tolerated. It is eliminated by the combination of glomerular filtration and active renal tubular secretion. Thus, it can be responsible, in the medium and long term, of renal toxicity. The aim of our study is to assess the prevalence of TDF nephrotoxicity and its factors risk in PLHIV treated in the Infectious Diseases Department at the University Hospital of Monastir, Tunisia..
 Methods: An observational cross-sectional single-centre prospective study included 62 cases of HIV-infected patients taking antiretroviral therapy (ART) containing TDF was conducted between 1st August 2016 and 31 December 2016 at Fattouma Bourguiba University Hospital of Monastir, in Tunisia. During this period, patients were screened for renal dysfunction to detect renal toxicity, Tubular dysfunction or Fanconi syndrome.
 Results: 62 patients were included with female/male ratio at 1,52. The mean age was 39 years ± 8,5 years. Half of the patients were treated with TDF as first-line therapy. The average duration of TDF was 25 months, the duration was greater than 12 months in 40 (65%) patients. There was a decrease in creatinine clearance in 21 (33.8%) patients, the average of the decrease was 128,6 ±35,8 ml/min Proximal tubulopathy was noted in 1 patient (1.6%) and no patient had Fanconi syndrome.
 No risk factors for renal impairment under TDF were found. This finding could be explained by the small sample size
 Conclusion: TDF-related renal toxicity is often asymptomatic, it require early detection. In ours patient cases, TD is rare, but creatinine clearance decrease is frequent and may inform of possible TD in these patient. In order to reduce TDFtoxicity, a new pro-drug, tenofovir alafenamide (TAF), is now available.

Assessment of renal safety of tenofovir disoproxil fumarate in people living with HIV in Tunisia

Background: Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor (NRTI). TDF is generally well tolerated. It is eliminated by the combination of glomerular filtration and active renal tubular secretion. Thus, it can be responsible, in the medium and long term, of renal toxicity. The aim of our study is to assess the prevalence of TDF nephrotoxicity and its factors risk in PLHIV treated in the Infectious Diseases Department at the University Hospital of Monastir, Tunisia..
 Methods: An observational cross-sectional single-centre prospective study included 62 cases of HIV-infected patients taking antiretroviral therapy (ART) containing TDF was conducted between 1st August 2016 and 31 December 2016 at Fattouma Bourguiba University Hospital of Monastir, in Tunisia. During this period, patients were screened for renal dysfunction to detect renal toxicity, Tubular dysfunction or Fanconi syndrome.
 Results: 62 patients were included with female/male ratio at 1,52. The mean age was 39 years ± 8,5 years. Half of the patients were treated with TDF as first-line therapy. The average duration of TDF was 25 months, the duration was greater than 12 months in 40 (65%) patients. There was a decrease in creatinine clearance in 21 (33.8%) patients, the average of the decrease was 128,6 ±35,8 ml/min Proximal tubulopathy was noted in 1 patient (1.6%) and no patient had Fanconi syndrome.
 No risk factors for renal impairment under TDF were found. This finding could be explained by the small sample size
 Conclusion: TDF-related renal toxicity is often asymptomatic, it require early detection. In ours patient cases, TD is rare, but creatinine clearance decrease is frequent and may inform of possible TD in these patient. In order to reduce TDFtoxicity, a new pro-drug, tenofovir alafenamide (TAF), is now available.

Prevalence, evolution, and related risk factors of kidney disease among Spanish HIV-infected individuals.

Prevalence of kidney disease (KD) is increasing among human immunodeficiency virus (HIV)-infected population. Different factors have been related, varying on different published series.The objectives were to study prevalence of KD in those patients, its evolution, and associated risk factors.An observational cohort study of 1596 HIV-positive patients with cross-sectional data collection in 2008 and 2010 was conducted. We obtained clinical and laboratory markers, and registered previous or current treatment with tenofovir (TDF) and indinavir (IDV). The sample was divided according to estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) equation. Group 1: eGFR ≤60 mL/min/1.73 m2; group 2: eGFR >60 mL/min/1.73 m2.Among the patients, 76.4% were men, mean age (SD) 45 ± 9 years, time since diagnose of HIV 14 ± 7 years, and 47.2% of the patients received previous treatment with TDF and 39.1% with IDV. In 2008, eGFR ≤60: 4.9% (91.4% of them in chronic kidney disease [CKD] stage 3, eGFR 59–30 mL/min); this group was older, presented higher fibrinogen levels, and more patients were treated previously with TDF and IDV. In 2010, eGFR ≤60: 3.9% (87.1% stage 3 CKD). The 2.4% of cohort showed renal improvement and 1.3% decline of renal function over time. The absence of hypertension and treatment with TDF were associated with improvement in eGFR. Increased age, elevated fibrinogen, decreased albumin, diabetes mellitus, hyperTG, and worse virological control were risk factors for renal impairment.The HIV-positive patients in our area have a CKD prevalence of 4% to 5% (90% stage 3 CKD) associated with ageing, inflammation, worse immune control of HIV, TDF treatment, and metabolic syndrome.

Intestinal failure as a significant risk factor for renal impairment in children.

Although impaired renal function has been a frequent finding among adults with intestinal failure (IF), the data on children is scarce. The aim of this study was to assess renal function in pediatric-onset IF. Medical records of 70 patients (38 boys) with pediatric-onset IF due to either short bowel syndrome (n=59) or primary motility disorder (n=11) and a history of parenteral nutrition (PN) dependency for ≥1mo were evaluated. Renal function at the most recent follow-up was studied using plasma creatinine, cystatin C, and urea concentrations and estimated glomerular filtration rate (eGFR). At a median age of 5.7y and after PN duration of 3.2y, 20 patients (29%) had decreased eGFR and higher cystatin C and urea concentrations. Patients with decreased renal function had significantly longer duration of PN (3.2 versus 0.9y; P=0.030) and shorter percentage of age-adjusted small bowel length remaining (22 versus 32%; P=0.041) compared with patients with preserved renal function. No other predisposing factors for decreased eGFR were identified. Patients with pediatric-onset IF are at significant risk for impaired renal function, which is associated with the duration of PN and the length of the remaining small bowel. In the present study, no other predisposing factors for decreased eGFR were found. Further studies using measured GFR are needed.

The relationship between obstructive sleep apnea hypopnea syndrome and renal function in patients with type 2 diabetes mellitus

Objective To observe the effect of obstructive sleep apnea hypopnea syndrome (OSAHS) on the renal function in patients with type 2 diabetes mellitus (T2DM). Methods Sleep apnea hypopnea index (AHI), oxygen desaturation index (ODI), and nighttime lowest oxygen saturation (LSaO2) were evaluated in 298 patients with T2DM using a portable sleep apnea monitor. Patients were divided into T2DM without OSAHS group (n=120) and with OSAHS group (n=178) according to AHI 90 ml·min-1·(1.73 m2)-1 (n=190), 90>eGFR>60 ml·min-1·(1.73 m2)-1 (n=84), eGFR<60 ml·min-1·(1.73 m2)-1 (n=24). The influencing factors of eGFR and AHI were analyzed by logistic regression analysis. Results There were significant differences in eGFR, uric acid (UA), high density lipoprotein-cholesterol (HDL-C), waist circumference, hip circumference, body mass index (BMI), and urinary albumin between T2DM without OSAHS and with OSAHS groups(all P<0.05). eGFR showed a significant correlation with AHI(r=-0.154, P=0.008), ODI(r=-0.236, P<0.01), and LSaO2(r=0.145, P=0.024). Logistic regression revealed that eGFR(OR=0.991, 95%CI 0.983~0.998, P=0.014), BMI(OR=1.107, 95%CI 1.028~1.193, P=0.008)were independent risk factors for AHI. There were significant differences in age, urinary albumin, AHI, ODI, LSaO2 among groups with various eGFR levels (P<0.05). Stepwise regression showed that age(β=-0.456, 95%CI -0.571~-0.346, P<0.01)and AHI(β=-0.119, 95%CI -0.226~-0.007, P=0.037) were independent risk factors for eGFR. Conclusions OSAHS is a risk factor for renal impairment in patients with T2DM. (Chin J Endocrinol Metab, 2017, 33: 552-555) Key words: Obstructive sleep apnea hypopnea syndrome; Diabetes mellitus, type 2; Chronic kidney disease

Identification of patients at risk for renal impairment after living donor kidney transplantation.

Outcome after living donor kidney transplantation is highly relevant, since recipient and donor were exposed to notable harm. Reliable identification of risk factors is necessary. Three hundred sixty-six living donor kidney transplants were included in this observational retrospective study. Relevant risk factors for renal impairment 1year after transplantation and delayed graft function were identified with univariable and multivariable binary logistic regression and ordinal regression analysis. Eighty-four patients (26.6%) suffered from renal impairment KDIGO stage ≥4 1year post-transplant; median estimated glomerular filtration rate was 35.3ml/min. In multivariable ordinal regression, male recipient sex (p < 0.001), recipient body mass index (p = 0.006), donor age (p = 0.002) and high percentages of panel reactive antibodies (p = 0.021) were revealed as independent risk factors for higher KDIGO stages. After adjustment for post-transplant data, recipient male sex (p < 0.001), donor age (p = 0.026) and decreased early renal function at the first post-transplant outpatient visit (p < 0.001) were identified as independent risk factors. Delayed graft function was independently associated with long stay on the waiting list (p = 0.011), high donor body mass index (p = 0.043), prolonged warm ischemic time (p = 0.016) and the presence of preformed donor-specific antibodies (p = 0.043). Broadening the donor pool with non-blood related donors seems to be legitimate, although with respect to careful medical selection, since donor age in combination with male recipient sex were shown to be risk factors for decreased graft function. Warm ischemic time and waiting time need to be kept as short as possible to avoid delayed graft function. Transplantation across HLA and ABO borders did not affect outcome significantly.

Prevalence of Renal Impairment in Patients With Rheumatoid Arthritis: Results From a Cross-Sectional Multicenter Study.

To assess the prevalence and associations of renal dysfunction in patients with rheumatoid arthritis (RA). COMEDRA is a French nationwide cross-sectional multicenter study on comorbidities in RA. Renal function was assessed from the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation. RA characteristics and risk factors for renal impairment were collected. Two logistic regression models, 1 with and 1 without the Framingham Risk Score, were constructed from variables that were significantly associated with an eGFR of <60 ml/minute/1.73 m(2) or were clinically relevant. Of the 970 recruited patients, 931 were analyzed (women 79.6%, mean age 57.8 years, disease duration 11.1 years, Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] 3.1). A total of 82 patients (8.8%) had an eGFR <60 ml/minute/1.73 m(2) and 9% had proteinuria. In univariate analysis, renal impairment was associated with age (P < 0.001), history of hypertension (P < 0.001), high systolic blood pressure (P = 0.03), and the Systematic Coronary Risk Evaluation (SCORE) equation (P = 0.002), but not with sex, disease duration, disease activity (as assessed by DAS28-ESR), nonsteroidal antiinflammatory drug use, disease severity (erosions, joint replacement), or RA medications. Multivariate analysis models showed that age (odds ratio [OR] 1.05 [95% confidence interval (95% CI) 1.03-1.09]) and hypertension (OR 2.5 [95% CI 1.5-4.3]) were associated with renal impairment. A second model showed that the SCORE equation (OR 1.33 [95% CI 1.06-1.67]) was associated with renal impairment. Renal impairment is relatively common in RA and is associated with cardiovascular risk factors such as age, hypertension, and the SCORE equation but not with disease activity or severity.

Prevalence and Risk Factors of Renal Impairment among Rheumatoid Arthritis Patients Attending Outpatient Department of Tikur Anbessa Specialized Hospital

Background: The global burden of chronic degenerative disease is increasing worldwide. Most developing countries have dual burden with infectious and non-infectious diseases. Kidney disease is a long term health condition and defined as the gradual loss of body, renal function and death over time. Renal abnormalities were quite prevalent in rheumatoid arthritis patients and there is a significant increase of renal derangement with duration of disease and severity of disease activity. Methods: A hospital based cross-sectional study was conducted. Blood sample was collected for assessment of urea and creatinine. Urine sample was also collected for protein and blood detection. Serum creatinine was analyzed by an automated biochemistry machine Mindray 200 BS. Urine protein and blood was detected by chemical test. Descriptive, bivariate and multivariate analyses were used to analyze the data. Odds ratio with 95%CI was estimated to assess the predictors of renal impairment. Result: Out of 219 rheumatoid arthritis patients, 49 (22.4%) had renal impairment. Serum creatinine level in mg/dl of the patients were with mean and standard deviation (SD) of (1.67 ± 0.47 SD) with adjusted odd ratio (AOR) and (95%CI):14.07 (5.09, 38.91), Mean (± SD) age of the participants was 43.82 (± 14.03) years and about 75.3% were females. Protienuria 44 (20.1%) with AOR (95%CI):1.93 (1.68, 5.58) and Body Mass Index (BMI) above 25 with AOR (95%CI): 0.1 (0.02, 0.45) shows significant association with the prevalence of renal impairment. Conclusion: The study revealed that the prevalence of renal impairment in patients’ with rheumatoid arthritis is high. Screening for renal impairment for patients with rheumatoid arthritis will be very helpful to peak kidney disease at earlier stage.

372PD Reduction in nephrotoxicities using short hydration in chemotherapy containing cisplatin: a consecutive analysis of 467 patients with thoracic malignancies

Aim/Background: Short hydration (SH) in chemotherapy containing cisplatin (CDDP) has become widespread in recent years. However, few large studies have reported the superiority of this method, compared with conventional hydration (CH), in terms of nephrotoxicities. Methods: We conducted a consecutive retrospective analysis of 467 patients with thoracic malignancies who had been treated with chemotherapy including CDDP between December 2009 and December 2013 at the National Cancer Center Hospital. All the cases had received aprepitant, 5-HT3 blocker and dexamethasone based on the antiemetic guidelines. Statistical analyses were performed to understand the risk factors for renal impairment after the administration of CDDP. The factors included in the analyses were as follows; age, sex, ECOG performance status (PS), concomitant thoracic radiotherapy, the dose of CDDP, degree of gastrointestinal adverse events, Mg supplementation, baseline creatinine (Cr) values, and method of hydration. Results: The patients' characteristics were as follows: male/female, 323/145 patients; median age (range), 62 (27-69) years; PS 0/1/2/3, 238/217/10/2 patients; and SH/CH, 111/356 patients. CDDP was administered with vinorelbine, pemetrexed, irinotecan, etoposide, docetaxel, gemcitabine or amurubicin (175, 148, 62, 34, 33, 13, and 2 cases, respectively). The percentage of patients requiring a dose reduction of CDDP in the SH group was 6.3%, while that in the CH group was 12.9%. The proportion of CDDP discontinuation because of nephrotoxicities was 0.9% in the SH group and 2.2% in the CH group. After CDDP-based chemotherapy, a Cr increase of more than Grade1 was found in 14.4% and 33.1% of the patients in the SH and CH groups, respectively, and the median estimated GFR values (mL/min/1.73m2) were 73.7 and 65.3, respectively. A logistic regression analysis revealed a significantly lower incidence of Grade 1 or higher Cr toxicity after the first cycle of CDDP based chemotherapy in the SH group(OR, 0.19; 95% confidence interval, 0.06-0.61; P = 0.006). Conclusions: Short hydration resulted in a significantly lower incidence of nephrotoxicity in CDDP-containing regimens. Disclosure: Y. Goto: membership on an advisory board or board of directors Lilly, Boehringer Ingelheim, Taiho. Y. Ohe: membership on an advisory board or board of directors Chugai, AstraZeneca, Lilly, Boehringer Ingelheim, Novartis, ONO, BMS. All other authors have declared no conflicts of interest.

Antiretroviral Treatment Efficacy and Safety in Older HIV-Infected Adults.

Highly active antiretroviral therapy (ART) and its widespread availability have revolutionized the landscape of HIV care and patient outcomes, transforming infection with HIV into a manageable chronic condition rather than a life-limiting disease. This transformation has created an older patient demographic. The effect that older age has on the outcomes of ART is not completely understood. Limited data are available in older individuals due to underrepresentation in clinical trials. To better understand this relationship, we conducted a literature search to assess the impact of older age on the outcomes of ART in the older HIV-infected population, including immunologic and virologic outcomes, mortality, disease progression, toxicity of ART, and pharmacokinetic considerations. In addition, package inserts of antiretroviral (ARV) medications were reviewed for efficacy, safety, and pharmacokinetic information pertaining to the older population. Most studies in older adults (50yrs or older) demonstrated slower and blunted CD4 immune recovery but better virologic suppression in response to ART. Higher rates of mortality and faster disease progression have been observed in adults 50 years and older, particularly during the first year after ART initiation. HIV-infected patients aged50years and older appear to be at greater risk for certain ART-associated toxicities including nephrotoxicity, decline in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction. The available literature suggests that clinicians should consider avoiding agents such as tenofovir disoproxil fumarate (TDF) in older patients with risk factors for renal impairment and/or osteoporosis. If TDF is used in patients aged50years or older, more frequent monitoring should be considered. Older age was a significant predictor for higher atazanavir exposure and higher lopinavir trough concentration at 24weeks. The clinical implications of these findings are unknown. It is imperative that future development of novel ARV drug therapies includes a greater proportion of older subjects in clinical trials.

Prevalence of macro- and microvascular complications in patients with type 2 diabetes and kidney disease with or without albuminuria in a single Chinese Diabetes Centre.

To investigate the relationship between diabetic retinopathy, neuropathy and low ankle-brachial index in mild-to-moderate chronic kidney disease of type 2 diabetic patients. We enrolled 875 type 2 diabetic patients who were divided into two phenotypes (with or without albuminuria) and stratified into three groups (stage 1 with estimated glomerular filtration rate ⩾ 90 mL/min/1.73 m(2), stage 2 with estimated glomerular filtration rate of 60-89, stage 3 with estimated glomerular filtration rate of 30-59). The prevalence of diabetic retinopathy, neuropathy and low ankle-brachial index was compared and the risk factors of renal impairment were determined. Among chronic kidney disease stages, the prevalence of diabetic retinopathy increased from 42.5%, 56.6% to 66.7% in albuminuric subjects and from 29.4%, 33.0% to 50.0% with no significant trend in normoalbuminuric subjects (p = 0.005, 0.007 and 0.399 compared with albuminuric subjects in each stage). There was a significantly increased prevalence of low ankle-brachial index (17.5%, 22.6% and 44.4%) in normoalbuminuric subjects but no significant trend in albuminuric subjects. Diabetic retinopathy (odds ratio = 2.474, 95% confidence interval = 1.009-6.068) was an independent risk factor of declining kidney function in albuminuric patients. The prevalence of diabetic retinopathy was graded according to the estimated glomerular filtration rate declining in albuminuric patients while the prevalence of low ankle-brachial index was gradually increased in normoalbuminuric patients, indicating the diverse underlying mechanisms of mild to moderate chronic kidney disease between these two phenotypes.

Adefovir- or Lamivudine-Induced Renal Tubular Dysfunction after Liver Transplantation.

To reduce hepatitis B virus reinfection after liver transplantation (LT), patients often receive antihepatitis B immunoglobulin (HBIG) alone or combined with antiviral nucleoside/nucleotide analogs (NUCs); however, proximal renal tubular dysfunction (RTD) that was induced by NUCs in liver recipients was rarely reported. Here, we analyzed RTD and renal impairment (RI) following adefovir (ADV) and lamivudine (LAM) treatment in liver recipients.We retrospectively reviewed medical records of patients treated with HBIG alone (group 1, n = 42) or combined with ADV or LAM (group 2, n = 21) after LT. We compared RTD and RI incidence during the 12 months after LT. An RTD diagnosis required manifestation of at least 3 of the following features: hypophosphatemia, RI, hypouricemia, proteinuria, or glucosuria.No significant differences were observed regarding sex, age, donor type, model of end-stage liver score, and estimated glomerular filtration rate at pre-LT between the 2 groups. Hepatitis B virus recurrence within 12 months was 4.8% in both groups (P = 1.000); however, the RTD incidence was 0% in group 1 and 19.0% in group 2 (P = 0.010). RI occurrence did not differ between the groups. The only risk factor for RI was HBIG administration combined with both LAM and ADV (odds ratio 11.27, 95% confidence interval 1.13–112.07, P = 0.039, vs HBIG alone).RTD occurred more frequently in patients treated with HBIG combined with LAM or ADV compared with HBIG alone. Thus, LAM or ADV therapy can induce RTD after LT, and when administered, liver recipients should be monitored.

Acute kidney injury after transcatheter aortic valve implantation.

Even though experience and techniques have constantly improved over the last years, peri- and postprocedural complications in high risk TAVI-collectives remain a major issue affecting outcome and survival. Acute kidney injury (AKI) is a frequent complication after transcatheter aortic valve implantation (TAVI) and effects outcome and survival. However, the definition of AKI in published studies dealing with the phenomenon of AKI after TAVI varies widely and lacks standardization. This Review aims to present an overview over the current literature concerning AKI after TAVI with regard to the definition of AKI, the impact of AKI on mortality and potential risk factors for renal impairment after TAVI.

Clinical Research about Risk Factors and Reversible Predictors in Renal Impairment due to Multiple Myeloma

This study was aimed to investigate the risk factors of renal impairment and the predictive factors of renal function recovery so as to provide basis for its prevention and treatment. Medical records of 161 patients with MM firstly diagnosed from January 2007 to April 2013 were analyzed retrospectively. Among them 58 cases accompanied with renal insufficiency (group A, others belong to group B) and 39 of them regain normal renal function after some treatment. The possible related renal impairment risk factors and reversible predictors were analyzed with chi-square test for significance firstly, then factors that have significant difference were entered into multivariate logistic regression analysis. Systolic blood pressure (SBP), hemoglobin, uric acid, blood calcium, phosphorus, serum β2-microglobulin, urine β2-microglobulin levels, M-component type, light chain type, nephrotoxic drug use, infection in group A had significant difference (P<0.05) compared with those in group B; the systolic blood pressure, diastolic blood pressure, platelet, globulin, blood calcium, and urine β2-microglobulin levels, the chemotherapy applied and the response to chemotherapy in reversed group were significantly different from no-reversed group (P<0.05). Multivariate logistic regression showed that light chain type, Hb, uric acid, Ca were the independent risk factors for the development of renal failure in MM, and Ca, chemotherapy and the response to chemotherapy were the predictors of renal function recovery. High blood calcium, severe anemia, λ light chain, high uric acid are the independent risk factors of renal impairment in MM patients. Patients with high blood calcium before treatment easily regain normal renal function after effective chemotherapy. Bortezomib-based chemotherapy has higher response rate and higher reversal rate, and it may be related with its unique mechanism.

Long-term renal function in unilateral non-syndromic renal tumor survivors treated according to International Society of Pediatric Oncology protocols.

The risk of renal impairment among survivors of childhood unilateral non-syndromic renal tumors (RTs) is not well defined. We evaluated the prevalence of and possible risk factors for renal impairment by estimating Glomerular Filtration Rate (eGFR) categories and chronic kidney disease (CKD) according to Kidney Disease: Improving Global Outcomes guidelines. Since 1978, 82 patients were treated for RT, according to the International Society of Pediatric Oncology protocols in a single oncology unit. Of the 67 survivors, those who underwent nephron sparing surgery, those with short-term follow-up or those who had bilateral and/or syndromic disease or a second malignancy were excluded. Thirty-five adult survivors (14 M/21F; mean age 25 years; mean follow-up 20 years) were studied by chemistry, kidney ultrasound, blood pressure measurement, urinanalysis. Correlations were investigated between the prevalence of eGFR categories and CKD and gender, age at diagnosis, radiotherapy, chemotherapy, body mass index, time of follow-up, and age at study. Eight (22.9%) survivors presented a mildly decreased eGFR (G2 category), the mean value was 80 ± 9.78 ml/min/1.73m(2) (median 84.5, range 63-89). Three (8.6%) survivors had CKD and a fourth (2.9%) hypertension. No significant correlations between G2 category and clinical variables were found. A small percentage of survivors had CKD or hypertension after two decades. It is not yet clear whether a mildly decreased eGFR that does not constitute CKD in the absence of other markers (albuminuria and/or kidney ultrasound abnormalities) is likely to progress to CKD. Health promotion programs to avoid comorbidities are required.

Serum creatinine concentration in very-low-birth-weight infants from birth to 34-36 wk postmenstrual age.

Background:Serum creatinine (s[Cr]) reference ranges for very-low-birth-weight (VLBW) infants must account for physiologic changes in the first months of life.Methods:We retrospectively identified a sample of 218 appropriate-for-gestational age (GA) VLBW infants without risk factors for renal impairment, and classified into one of three GA groups: 25–27, 28–29, and 30–33 wk. We observed three phases of s[Cr] change (initial, decline, and equilibrium), whose characteristics varied by GA group. We used mixed-effects regression models to estimate mean and upper 95th prediction interval of s[Cr] for each GA group from birth to 34–36 wk post menstrual age (PMA).Results:In phase I, s[Cr] increased after birth, then returned slowly to baseline. The duration of phase I and the magnitude of s[Cr] rise decreased with increasing GA. In phase II, s[Cr] declined abruptly at a rate that increased with GA. A gradual transition to phase III, a steady-state equilibrium with similar s[Cr] among GA groups, began at approximately 34–36 wk PMA. We constructed GA group-specific nomograms depicting s[Cr] behaviour across the three phases.Conclusion:The reference ranges derived from a sample of infants without risk factors for renal impairment provide a context for quantitative interpretation of s[Cr] trends in VLBW infants.

Reanalysis of membranoproliferative glomerulonephritis patients according to the new classification: a multicenter study

BackgroundAll types of membranoproliferative glomerulonephritis (MPGN) are progressive diseases with poor prognoses. Recently, a newly proposed classification of these diseases separated them into immune complex- and complement-mediated diseases. We investigated the frequency of C3 glomerulonephritis among previously diagnosed MPGN patients. MethodsWe conducted a retrospective study of patients diagnosed with MPGN at three tertiary care institutions between 2001 and 2010. We investigated the incidence of complement-mediated disease among patients diagnosed with MPGN. Progressive renal dysfunction was defined as a 50% reduction in the glomerular filtration rate or the need for renal replacement therapy. ResultsAmong the 3,294 renal biopsy patients, 77 (2.3%) were diagnosed with MPGN; 31 cases were excluded, of which seven were diagnosed with systemic lupus nephritis, and the others were not followed for a minimum of 12 months after biopsy. Based on the new classification, complement-mediated MPGN was diagnosed in two patients (4.3%); only one patient developed progressive renal dysfunction. Among the immune complex-mediated MPGN patients, 17 patients developed progressive renal dysfunction. Serum albumin and creatinine levels at the time of MPGN diagnosis were risk factors of renal deterioration, after adjusting for low C3 levels and nephrotic syndrome. ConclusionComplement-mediated glomerulonephritis was present in 4.3% of patients previously diagnosed with MPGN.

Renal impairment is frequent in chronic hepatitis C patients under triple therapy with telaprevir or boceprevir

We read with great interest the article by Mauss et al. published in Hepatology.1 While renal impairment was not reported as a safety signal in phase III clinical trials, the authors alert our attention to a potential renal toxicity of first-generation antiproteases administered with peginterferon and ribavirin, especially in patients with risk factors for renal impairment. They demonstrate in telaprevir-treated patients a significant decrease of enhanced glomerular filtration rate (eGFR) (CKD EPI formula) during the first 12 weeks of treatment, but this decrease was early and completely reversible after discontinuation of the drug, before the 24th week of treatment. Comprehension of the mechanism of the decrease of eGFR is essential, as it might change monitoring of the patients. In a recent article, Kunze et al.2 showed that interactions of telaprevir with drug transporters should not be neglected: telaprevir was shown to inhibit mostly the human renal drug transporter OCT2 (basal membrane of tubular cell), which interacts with creatinin tubular transport and is included in proximal tubular secretion. Recently, Raffi et al.,3 studying the efficacy and safety profile of both dolutegravir and raltegravir in human immunodeficiency virus (HIV)-infected patients, showed an increase of creatinin level only with dolutegravir. Dolutegravir and not raltegravir inhibits OCT2, which leads to a decrease of tubular secretion of creatinin and therefore increases concentrations of serum creatinin without affecting glomerular filtration. This inhibition of tubular secretion of creatinin has also been described with other antiretrovirals (ARVs), trimethoprim and cimetidine. By analogy, the rapid and reversible decrease of calculated eGFR during telaprevir therapy could be due to the same mechanism involving OCT2. Even if we cannot provide proof of this hypothesis, we suggest that a mild or moderate reversible initial decrease of eGFR with telaprevir therapy is not always due to renal toxicity. However, as true renal toxicity may occur during treatment with peginterferon, ribavirin and potentially protease inhibitors, a careful monitoring of eGFR should be performed during all treatment. In our experience (not published data), the decrease of eGFR under telaprevir is quick, with a nadir before week 8 (20% on average) and is completely reversible after week 12. We suggest referring the patient to a nephrologist if the eGFR decreases for more than 20% before week 8 and goes on decreasing after, or does not increase after cessation of therapy. Future studies concerning second-generation hepatitis C virus (HCV) direct antiviral drugs should take into account this potential decrease of eGFR. Véronique Loustaud-Ratti, M.D.1,2 Paul Carrier, M.D.1 Chanlina Vong, M.D.1 Marie Essig, M.D., Ph.D.3,4 1Fédération d'Hépatologie, Service d'Hépato-gastroentérologie, Limoges, France 2Inserm UMR 1092, Faculté de Médecine de Limoges, Limoges, France 3Service de Néphrologie, Dialyse, Transplantation, Limoges, France 4Inserm UMR S850, Faculté de Médecine de Limoges, Limoges, France

Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) and kidney diseases: HCaRG accelerates tubular repair

Hypertension is a risk factor for renal impairment. While treatment of hypertension provides significant renal protection, there is still an unmet need requiring further exploration of additional pathogenetic mechanisms. We have found that the hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is involved in renal repair. HCaRG is a small intracellular protein of 225 amino acids and its gene expression is negatively regulated by extracellular calcium concentrations. HCaRG is mostly expressed in the kidneys, with higher levels found in the spontaneously hypertensive rat than in normotensive rats. In an acute kidney injury model, HCaRG expression decreases immediately after injury but increases above baseline during the repair phase. In cell cultures, HCaRG has been shown to facilitate differentiation and to inhibit cell proliferation via p21 transactivation through the p53-independent signaling pathway. Induction of p21 independently of p53 is also observed in transgenic mice overexpressing HCaRG during the repair phase after ischemia/reperfusion injury, resulting in their improved renal function and survival with rapid re-differentiation of proximal tubular epithelial cells. In addition, transgenic mice recover rapidly from the inflammatory burst most likely as a result of maintenance of the tubular epithelial barrier. Recent studies indicate that facilitating re-differentiation and cell cycle regulation in injured renal proximal tubules might be important functions of HCaRG. We have proposed that HCaRG is a component of differential genetic susceptibility to renal impairment in response to hypertension.

Antiretroviral therapy, immune suppression and renal impairment in HIV-positive persons

The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field. Several individual antiretroviral agents (ARVs) including tenofovir and several protease inhibitors have, in diverse study settings, been associated with renal impairment. Traditional renal risk factors are common among those experiencing adverse renal impairment to ARVs, but do not fully explain why only some develop these effects. Discontinuation of nephrotoxic ARVs is common with declining renal function, but has unknown long-term consequences. Immune suppression is a strong independent risk factor for renal impairment, and ongoing investigations will clarify whether initiating ARVs with nephrotoxic properties at higher CD4 cell counts will have net beneficial effects on renal function. With improvements in survival, multiple risk factors have emerged for renal impairment in HIV-positive persons. Although certain ARVs may cause moderate renal impairment, effects on more severe renal impairment remain unresolved. Regular renal function monitoring allow for switching away from nephrotoxic ARVs in case of decreasing function. If such actions prove beneficial higher prevalence of ARV-associated severe renal impairment may emerge in populations without access to regular monitoring.