Visceral leishmaniasis-associated nephropathy in hospitalised Brazilian patients: new insights based on kidney injury biomarkers.

OBJECTIVE: To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis. METHODS: Prospective study with 50 hospitalised VL patients. AKI biomarkers, that is, serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL, uNGAL, respectively), urinary kidney injury molecule-1 (uKIM-1) and urinary monocyte chemotactic protein-1 (uMCP-1), were quantified by immunoassay (ELISA). Also, interferon-gamma (INF-y) and C-reactive protein (CRP) were evaluated as inflammatory biomarkers possibly related to VL severity. RESULTS: VL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia, haematologic and hepatic disorders. AKI was found in 46%, and one death (2%) occurred. The AKI group had significant longer hospital stay, lower levels of IFN-y and higher levels of CRP, more clinical renal abnormalities and higher levels of sNGAL, uNGAL, uKIM-1 and uMCP-1. Overall, sNGAL, uKIM-1 and uMCP-1 showed correlations with important clinical renal abnormalities, such as proteinuria, albuminuria, serum creatinine and glomerular filtration rate using adjusted correlations with CRP and IFN-y. Only sNGAL showed an early association with AKI development (OR = 2.78, 95% CI = 1.429-5.428, per each increase of 50 ng/ml), even after adjusting for clinical signals of VL severity and for immune biomarkers. Moreover, sNGAL showed a better performance in predicting AKI development (AUC-ROC = 0.81, 95% CI = 0.69-0.93; cut-off = 154 ng/ml, sensitivity = 82.6%, specificity = 74.1%, P < 0.001). CONCLUSIONS: Visceral leishmaniasis-associated nephropathy showed important proximal tubular injury and glomerular inflammation. Serum NGAL showed an early association with VL-associated nephropathy and may be used to improve clinical management strategies and decrease morbimortality in VL patients.

Quantitative Renal Echogenicity as a Tool for Diagnosis of Advanced Chronic Kidney Disease in Patients with Glomerulopathies and no Liver Disease.

BACKGROUND/AIMS: Glomerulopathy patients are prone to developing transitory reduced glomerular filtration rate (GFR), which can be difficult to differentiate from irreversible chronic kidney disease (CKD). Renal ultrasound can be useful, but differently from renal length, quantitative renal echogenicity has not been formerly evaluated regarding its capacity to identify irreversible advanced CKD. METHODS: A prospective study was performed, where quantitative renal echogenicity was performed during renal biopsy in patients with suspected glomerular disease (n=197). Quantitative echogenicity was measured as the inverse of the ratio between the mean pixel densities of the renal cortex and adjacent liver using ScionImage software. Patients were followed during a six-months period to ascertain irreversible advanced CKD. Quantitative renal echogenicity and histopathology parameters discriminatory capacity were compared regarding their capacity to detect advanced and irreversible CKD - estimated GFR less than 30mL/min/1.73m2 confirmed after a six-month follow-up. RESULTS: At renal biopsy, the mean eGFR was 53.9±33.6 mL/min/1.73m2 and 63 (32.0%) patients had an eGFR less than 30 mL/min/1.73m2. Mean kidney/liver echogenicity ratio was 1.06±0.19 and it was inversely correlated with eGFR at follow-up (r=-0.684, p<0.001). Multivariate analysis was performed to create a histopathology index that correctly identifies irreversible advanced CKD. Renal echogenicity discriminatory capacity to identify irreversible advanced CKD was 0.793 (0.719 -0.867), similar to the histopathology index. Elevated renal echogenicity with best discriminatory capacity was a kidney/liver ratio greater than 1.15. This cutoff had a predictive positive value of 92% in patients with eGFR less than 30mL/min/1.73m2. CONCLUSION: Quantitative renal echogenicity can be a useful tool in patients with glomerular disease and normal kidney size (>8cm) to identify those patients with irreversible advanced CKD.

Lactated Ringer Is Associated With Reduced Mortality and Less Acute Kidney Injury in Critically Ill Patients: A Retrospective Cohort Analysis.

OBJECTIVES: To assess the impact of the percentage of fluid infused as Lactated Ringer (%LR) during the first 2 days of ICU admission in hospital mortality and occurrence of acute kidney injury. DESIGN: Retrospective cohort. SETTING: Analysis of a large public database (Multiparameter Intelligent Monitoring in Intensive Care-II). PATIENTS: Adult patients with at least 2 days of ICU stay, admission creatinine lower than 5 mg/dL, and that received at least 500 mL of fluid in the first 48 hours. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: 10,249 patients were included in mortality analysis and 8,085 were included in the acute kidney injury analysis. For acute kidney injury analysis, we excluded patients achieving acute kidney injury criteria in the first 2 days of ICU stay. Acute kidney injury was defined as stage 2/3 Kidney Disease: Improving Global Outcomes creatinine criteria and was assessed from days 3-7. The effects of %LR in both outcomes were assessed through logistic regression controlling for confounders. Principal component analysis was applied to assess the effect of volume of each fluid type on mortality. Higher %LR was associated with lower mortality and less acute kidney injury. %LR effect increased with total volume of fluid infused. For patients in the fourth quartile of fluid volume (> 7 L), the odds ratio for mortality for %LR equal to 75% versus %LR equal to 25% was 0.50 (95% CI, 0.32-0.79; p < 0.001). Principal component analysis suggested that volume of Lactated Ringer and 0.9% saline infused had opposite effects in outcome, favoring Lactated Ringer. CONCLUSIONS: Higher %LR was associated with reduced hospital mortality and with less acute kidney injury from days 3-7 after ICU admission. The association between %LR and mortality was influenced by the total volume of fluids infused.

Fluid composition and acute kidney injury.

PURPOSE OF REVIEW: To describe recent advances in the understanding of the role of fluid composition in renal outcomes in critically ill patients. RECENT FINDINGS: The debate on fluid composition is now focused in a pragmatic discussion on fluid electrolyte composition. The resurgence of this debate was propelled by several observational studies that suggested that balanced (i.e., low chloride) solutions were associated with less acute kidney injury in critically ill patients. Nevertheless, a cluster randomized trial failed to show any benefit of balanced solutions. This trial, however, may have failed to detect an effect because of low global illness severity and little fluid infused. If balanced solutions are to be associated with less acute kidney injury, it will probably be in high risk, aggressively resuscitated patients. Additionally, the causal loop involving unbalanced solution infusion, induction of hyperchloremia and acute kidney injury is yet to be closed. Other factors, such as buffer type, speed of infusion and temperature, among others, may also be important. SUMMARY: Recent evidence suggests that crystalloid fluid composition matters and can influence renal outcomes in critically ill patients. Further studies should assess the impact and cost-efficiency of balanced solutions in the context of high-risk scenarios.

Gingerol fraction from Zingiber officinale protects against gentamicin-induced nephrotoxicity.

Nephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal damage by overproduction of reactive oxygen species and inflammation in proximal tubular cells. Phenolic compounds from ginger, called gingerols, have been demonstrated to have antioxidant and anti-inflammatory effects. We investigated if oral treatment with an enriched solution of gingerols (GF) would promote a nephroprotective effect in an animal nephropathy model. The following six groups of male Wistar rats were studied: (i) control group (CT group); (ii) gingerol solution control group (GF group); (iii) gentamicin treatment group (GM group), receiving 100 mg/kg of body weight intraperitoneally (i.p.); and (iv to vi) gentamicin groups also receiving GF, at doses of 6.25, 12.5, and 25 mg/kg, respectively (GM+GF groups). Animals from the GM group had a significant decrease in creatinine clearance and higher levels of urinary protein excretion. This was associated with markers of oxidative stress and nitric oxide production. Also, there were increases of the mRNA levels for proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-1ß [IL-1ß], IL-2, and gamma interferon [IFN-γ]). Histopathological findings of tubular degeneration and inflammatory cell infiltration reinforced GM-induced nephrotoxicity. All these alterations were attenuated by previous oral treatment with GF. Animals from the GM+GF groups showed amelioration in renal function parameters and reduced lipid peroxidation and nitrosative stress, in addition to an increment in the levels of glutathione (GSH) and superoxide dismutase (SOD) activity. Gingerols also promoted significant reductions in mRNA transcription for TNF-α, IL-2, and IFN-γ. These effects were dose dependent. These results demonstrate that GF promotes a nephroprotective effect on GM-mediated nephropathy by oxidative stress, inflammatory processes, and renal dysfunction.

Cancer patients under maintenance hemodialysis: relationship between quality of life, depression, sleep quality and malnutrition-inflammation score.

BACKGROUND: The kidney is one major organ affected by cancer and its associated therapies. The aim of this study was to compare the levels of depression, quality of life and sleep quality in hemodialysis patients with or without cancer, and to analyze the associations with the malnutrition-inflammation score (MIS). PATIENTS AND METHODS: In this cross-sectional study, 40 cancer patients under hemodialysis and 44 patients under hemodialysis without cancer who served as the control group were included. Participants underwent structured interviews to investigate depression, quality of life, sleep quality and restless legs syndrome. RESULTS: Hemodialysis patients with cancer had a greater depression score (16.5 ± 4.8 vs. 10.8 ± 5.2, p < 0.001). Patients had similar physical and mental composite quality of life scores. Patients under hemodialysis with cancer had poor quality of sleep (mean score 8.8 ± 3.5 vs. 6.4 ± 4.1, p = 0.011) and a higher prevalence of restless leg syndrome (55.9 vs. 25.7%, p = 0.011). These features were associated with MIS in patients without cancer but not in patients with cancer. CONCLUSION: Cancer patients undergoing hemodialysis present a higher prevalence of depression, poor quality of life, sleep disorders; however, associations of these features with MIS are different in hemodialysis patients with or without cancer. These findings can change the clinical approach to these patients.

Timing of renal replacement therapy initiation by AKIN classification system.

INTRODUCTION: Previous studies using Acute Kidney Injury Network (AKIN)/RIFLE criteria to classify early initiation of renal replacement therapy (RRT) have defined it as the therapy started in less severe AKIN/RIFLE stages. Generally, these studies failed in demonstrating measurable benefits. METHODS: We compared RRT initiation in critically ill patients and defined early or late RRT in reference to timing after stage 3 AKIN was met: patients beginning RRT within 24 hours after acute kidney injury (AKI) stage 3 were considered early starters. AKIN criteria were evaluated by both urine output (UO) and serum creatinine (sCr) and patients with acute-on-chronic kidney disease were excluded. A propensity score methodology was used to control variables. RESULTS: A total of 358 critically ill patients were submitted to RRT. Only 150 patients with pure AKI at stage 3 were analyzed. Mortality was lower in the early RRT group (51.5 vs. 77.9%, P=0.001). After achieving balance between the groups using a propensity score, there was a significant 30.5 (95% confidence interval [CI] 14.4 to 45.2%, P=0.002) relative decrease of mortality in the early RRT group. Moreover, patients on the early RRT group had lower duration of mechanical ventilation, time on RRT and a trend to lower intensive care unit (ICU) length of stay. CONCLUSIONS: For the first time, AKIN was used with UO criterion to evaluate early and late RRT. Using a time-based approach could be a better parameter to access the association between RRT initiation and outcomes in patients with AKI.

Renal tubular dysfunction in sickle cell disease.

BACKGROUND/AIMS: Kidney abnormalities are one of the main chronic complications of sickle cell disease (SCD). The aim of this study is to investigate the occurrence of renal tubular abnormalities among patients with SCD. METHODS: This is a prospective study with 26 SCD adult patients in Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl2), after a 12h period of water and food deprivation. Fractional excretion of sodium (FENa), transtubular potassium gradient (TTKG) and solute free water reabsorption (TcH2O) were calculated. The SCD group was compared to a group of 15 healthy volunteers (control group). RESULTS: Patient`s average age and gender were similar to controls. Urinary acidification deficit was found in 10 SCD patients (38.4%), who presented urinary pH >5.3 after CaCl2 test. Urinary osmolality was significantly lower in SCD patients (355 ± 60 vs. 818 ± 202 mOsm/kg, p=0.0001, after 12h period water deprivation). Urinary concentration deficit was found in all SCD patients (100%). FENa was higher among SCD patients (0.75 ± 0.3 vs. 0.55 ± 0.2%, p=0.02). The TTKG was higher in SCD patients (5.5 ± 2.5 vs. 3.0 ± 1.5, p=0.001), and TcH2O was lower (0.22 ± 0.3 vs. 1.1 ± 0.3L/day, p=0.0001). CONCLUSIONS: SCD is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating and incomplete distal acidification defect. There was also an increase in the potassium transport and decrease in water reabsorption, evidencing the occurrence of distal tubular dysfunction. .

Differences in community, hospital and intensive care unit-acquired acute kidney injury: observational study in a nephrology service of a developing country.

BACKGROUND: Acute kidney injury (AKI) complicates more than 7% of all in-hospital patients. The aim of this study is to investigate the differences in community, hospital and intensive care unit-acquired AKI in patients undergoing nephrology consultation in a tertiary hospital in a developing country. METHODS: An observational cohort study of all patients with AKI admitted to the General Hospital of Fortaleza, Brazil was conducted. RIFLE criteria were used to classify the patients and to assess their association with death. Univariate and multivariate analyses were performed to investigate the factors associated with death. RESULTS: Of 491 AKI patients undergoing nephrology consultation, the mean age was 55.2 ± 22.9 years. Community-acquired AKI was observed in 55% of cases, general ward-acquired in 29% and ICU-acquired in 15.3%. Late Nephrology consultation was observed, and the great majority of patients had "Failure" classification (90%) according to RIFLE criteria. Intermittent hemodialysis was required in 68% of cases. The overall in-hospital mortality was 23%. The in-hospital mortality was higher in ICU-acquired AKI (33.6%). Community acquired AKI had a higher mortality than general ward-acquired AKI (23% vs. 11.6%, p = 0.001). Risk factors for death were infection (OR = 2.0, p = 0.003), neoplasms (OR = 1.89, p = 0.042), community acquired-AKI (OR = 1.27, p = 0.003), ICU acquired-AKI (OR = 2.76, p < 0.0001) and need for renal replacement therapy (OR = 2.64, p < 0.001). CONCLUSIONS: AKI is a frequent and frequently fatal condition. Mortality was higher in community and ICU-acquired than hospital ward-acquired AKI.

Renal function evaluation in patients with American cutaneous leishmaniasis after specific treatment with pentavalent antimonial.

BACKGROUND: Renal evaluation studies are rare in American Cutaneous Leishmaniasis (ACL). The aim of this study is to investigate whether specific treatment reverts ACL-associated renal dysfunction. METHODS: A prospective study was conducted with 37 patients with ACL. Urinary concentrating and acidification ability was assessed before and after treatment with pentavalent antimonial. RESULTS: The patients mean age was 35.6 ± 12 years and 19 were male. Before treatment, urinary concentrating defect (U/Posm <2.8) was identified in 27 patients (77%) and urinary acidification defect in 17 patients (46%). No significant glomerular dysfunction was observed before and after specific ACL treatment. There was no reversion of urinary concentrating defects, being observed in 77% of the patients before and in 88% after treatment (p = 0.344). Urinary acidification defect was corrected in 9 patients after treatment, reducing its prevalence from 40% before to only 16% after treament, (p = 0.012). Microalbuminuria higher than 30 mg/g was found in 35% of patients before treatment and in only 8% after treatment. Regarding fractional excretion of sodium, potassium, calcium, phosphorus and magnesium, there was no significant difference between pre and post-treatment period. CONCLUSION: As previously described, urinary concentrating and acidification defects were found in an important number of patients with ACL. Present results demonstrate that only some patients recover urinary acidification capacity, while no one returned to normal urinary concentration capacity.

Renal tubular dysfunction in patients with American cutaneous leishmaniasis.

Renal dysfunction seen in patients with American cutaneous leishmaniasis (ACL) has been attributed to the use of antimonials for treatment. To determine whether ACL itself causes tubular dysfunction, we measured renal function in 37 patients with ACL prior to their treatment and compared results to that in 10 healthy volunteers of similar mean age. None of the patients presented with glomerular dysfunction; however, 27 had a urinary concentrating defect. There was no statistical difference between groups in the pre- and post-desmopressin test of urine osmolality, but the post-test urine osmolality of the controls was significantly higher. Urinary AQP2 levels, determined by western blot of isolated exosomes, were found to be significantly lower in patients than in controls, whereas that of the cotransporter (NKCC2) was significantly higher. A urinary acidification defect (post-test pH greater than 5.50 following calcium chloride) was found in 15 patients. Pretest plasma bicarbonate was below normal in 12 patients as was the pretest plasma pH in 14. Expression of the Na/H exchanger (NHE3), H(+)-ATPase, and pendrin were all significantly higher in patients with ACL than in controls. A combined urinary concentration and acidification defect was found in 12 patients. Thus, the urinary concentrating defect of ACL may be caused by decreased AQP2, with increased NKCC2 compensatory. Pendrin upregulation may be related to the urinary acidification defect with increased NHE3 and H(+)-ATPase also compensatory. Hence, ACL can cause asymptomatic renal tubular dysfunction.

Renal function improvement with pentavalent antimonial agents in patients with visceral leishmaniasis.

BACKGROUND: The aim of this study is to investigate tubular and glomerular function after visceral leishmaniasis (VL) treatment with pentavalent antimonials. METHODS: This is a prospective study including 14 patients with VL diagnosis treated with pentavalent antimonials. Urine acidification and concentration tests were performed. Estimated glomerular filtration rate (eGFR), fractional excretion of sodium (FE(Na)) and potassium (FE(K)) and free water clearance (C(H2O)) were measured to assess glomerular and tubular function. RESULTS: The VL group had a significantly lower FE(K), serum sodium and plasma osmolality (P(osm)). No significant differences were found regarding proteinuria, eGFR, FE(Na) or C(H2O). Patients in the VL group had lower urinary osmolality (U(osm)) before DDAVP use when compared to the control group, as well as a lower U/P(osm). The urinary pH before and after CaCl(2) load was higher in the VL group. CONCLUSION: This study shows evidence of reversal of some tubular dysfunction in VL, but other dysfunctions may persist, especially urinary acidification capacity.

RIFLE and Acute Kidney Injury Network classifications predict mortality in leptospirosis-associated acute kidney injury.

AIM: Acute kidney injury (AKI) is a common complication in leptospirosis. The aim of this study is to investigate the association between RIFLE and AKIN classifications with mortality in leptospirosis-associated AKI. METHODS: A retrospective study was conducted in patients with leptospirosis admitted to tertiary hospitals in Brazil. The association between RIFLE and AKIN classifications with mortality was investigated. Univariate and multivariate analysis was performed to investigate risk factors for death. RESULTS: A total of 287 patients were included, with an average age of 37 ± 16 years, and 80.8% were male. Overall mortality was 13%. There was a significant association between these classifications and death. Among non-survivors, 86% were in the class 'failure' and AKIN 3. Increased mortality was observed according to the worse classifications: 'risk' (R; 2%), 'injury' (I; 8%) and 'failure' (F; 23%), as well as in AKIN 1 (2%), AKIN 2 (8%) and AKIN 3 (23%) (P < 0.0001). The worst classifications were significantly associated with death: RIFLE F (odds ratio = 11.6, P = 0.018) and AKIN 3 (odds ratio = 12.8, P = 0.013). Receiver-operator curve for patients with AKI showed high areas under the curve (0.71, 95% confidence interval = 0.67-0.74) for both RIFLE and AKIN classifications in determining the sensitivity for mortality. CONCLUSION: There is a significant association between RIFLE and AKIN classifications with mortality in patients with leptospirosis. Initiation of dialysis in patients with RIFLE F and AKIN 3 should always be considered.

Metabolic acidosis in patients with severe sepsis and septic shock: a longitudinal quantitative study.

OBJECTIVE: To describe the composition of metabolic acidosis in patients with severe sepsis and septic shock at intensive care unit admission and throughout the first 5 days of intensive care unit stay. DESIGN: Prospective, observational study. SETTING: Twelve-bed intensive care unit. PATIENTS: Sixty patients with either severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were collected until 5 days after intensive care unit admission. We studied the contribution of inorganic ion difference, lactate, albumin, phosphate, and strong ion gap to metabolic acidosis. At admission, standard base excess was -6.69 +/- 4.19 mEq/L in survivors vs. -11.63 +/- 4.87 mEq/L in nonsurvivors (p < .05); inorganic ion difference (mainly resulting from hyperchloremia) was responsible for a decrease in standard base excess by 5.64 +/- 4.96 mEq/L in survivors vs. 8.94 +/- 7.06 mEq/L in nonsurvivors (p < .05); strong ion gap was responsible for a decrease in standard base excess by 4.07 +/- 3.57 mEq/L in survivors vs. 4.92 +/- 5.55 mEq/L in nonsurvivors with a nonsignificant probability value; and lactate was responsible for a decrease in standard base excess to 1.34 +/- 2.07 mEq/L in survivors vs. 1.61 +/- 2.25 mEq/L in nonsurvivors with a nonsignificant probability value. Albumin had an important alkalinizing effect in both groups; phosphate had a minimal acid-base effect. Acidosis in survivors was corrected during the study period as a result of a decrease in lactate and strong ion gap levels, whereas nonsurvivors did not correct their metabolic acidosis. In addition to Acute Physiology and Chronic Health Evaluation II score and serum creatinine level,inorganic ion difference acidosis magnitude at intensive care unit admission was independently associated with a worse outcome. CONCLUSIONS: Patients with severe sepsis and septic shock exhibit a complex metabolic acidosis at intensive care unit admission, caused predominantly by hyperchloremic acidosis,which was more pronounced in nonsurvivors. Acidosis resolution in survivors was attributable to a decrease in strong ion gap and lactate levels.

Predictors of oliguric acute kidney injury in leptospirosis. A retrospective study on 196 consecutive patients.

BACKGROUND: Acute kidney injury (AKI) occurs in 10 to 60% of patients with leptospirosis. The aim of this study is to investigate markers for oliguric AKI in leptospirosis. METHODS: A retrospective study was performed with 196 consecutive patients with leptospirosis-associated AKI. These patients were categorized into either oliguric or non-oliguric according to their urine output. Clinical and laboratory characteristics were compared between the two groups. RESULTS: Among these patients, 64 (32.6%) were oliguric and 132 (67.4%) nonoliguric. Markers for oliguria were age higher than 40 years (OR = 1.02, p = 0.04), hyponatremia (OR = 0.94, p = 0.03), elevated serum creatinine (OR = 1.11, p = 0.04), low arterial pH (OR = 1.0002, p = 0.01), high levels of AST (OR = 1.005, p = 0.01), crackles (OR = 3.83, p < 0.001) and direct bilirubin (OR = 1.03, p = 0.03). Elevated activated prothrombin time (OR = 0.97, p = 0.03) was a factor associated with nonoliguric AKI. Independent markers for oliguria were crackles (OR = 5.17, p = 0.0016) and direct bilirubin levels (OR = 1.051, p = 0.04). Mortality was significantly higher in oliguric than nonoliguric (27 vs. 8%, p < 0.001). Renal function at discharge was similar in oliguric and nonoliguric patients. CONCLUSION: Age higher than 40 years, hyponatremia, elevated serum creatinine, low arterial pH, high levels of AST, crackles and direct bilirubin levels would be useful to early identify patients with oliguric AKI in leptospirosis.

Quality of life assessment among haemodialysis patients in a single centre: a 2-year follow-up.

BACKGROUND: Prospective studies of the effects of long-standing haemodialysis (HD) on quality of life (QOL) show conflicting results. We investigated how QOL progresses over time in HD patients and what factors are associated with this evolution. METHODS: We included chronic HD patients over the age of 18 from a single unit, who had never had transplants and survived the first 3 months of treatment. Ninety-two patients were followed for 2 years, and the SF-36 questionnaire was administered at baseline and every 12 months. Comorbidity was assessed at baseline using the Khan index. We used repeated-measures analysis of variance to establish changes in QOL and stepwise linear regression to identify continuous variables that could explain variations of SF-36 sub-scales. Then, according to the rate of change of QOL, we stratified the sample to identify the association between categorical variables and the evolution of QOL. RESULTS: There was a higher (better) final score related to social functioning (63.8 vs. 75.0; P < 0.01), role-emotional (39.7 vs. 63.1; P < 0.01) and mental health (63.1 vs. 69.0; P < 0.01) in the all-sample analysis, and in two other domains in low-comorbidity patients: physical functioning (56.7 vs. 63.5; P = 0.01) and bodily pain (56.7 vs. 66.5; P < 0.01). Creatinine (r = 0.09; P = 0.04) and age (r = -0.03; P = 0.02) were correlated with the evolution of general health and bodily pain, respectively. There were more women who presented deteriorated physical function than men (50.0 vs. 21.2%; P < 0.01). CONCLUSIONS: There was improvement of QOL mental domains over time. However, the physical aspects improved only in low-comorbidity patients. More women than men worsened regarding physical functioning.

Rosiglitazone reverses tenofovir-induced nephrotoxicity.

Tenofovir disoproxil fumarate (TDF) is a first-line drug used in patients with highly active retroviral disease; however, it can cause renal failure associated with many tubular anomalies that may be due to down regulation of a variety of ion transporters. Because rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist induces the expression of many of these same transporters, we tested if the nephrotoxicity can be ameliorated by its use. High doses of TDF caused severe renal failure in rats accompanied by a reduction in endothelial nitric-oxide synthase and intense renal vasoconstriction; all of which were significantly improved by rosiglitazone treatment. Low-dose TDF did not alter glomerular filtration rate but produced significant phosphaturia, proximal tubular acidosis, polyuria and a reduced urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. A Fanconi's-like syndrome was ruled out as there was no proteinuria or glycosuria. Rosiglitazone reversed TDF-induced tubular nephrotoxicity, normalized urinary biochemical parameters and membrane transporter protein expression. These studies suggest that rosiglitazone treatment might be useful in patients presenting with TFV-induced nephrotoxicity especially in those with hypophosphatemia or reduced glomerular filtration rate.