Impaired Baseline Renal Function Research Articles

Acute kidney injury after endovascular therapy in acute stroke patients: systematic review with meta-analysis

AimsEndovascular therapy (EVT) is a highly effective stroke treatment, but it requires the administration of contrast media which puts patients at risk of acute kidney injury (AKI). AKI is associated...

Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury.

Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.

Impaired Baseline Renal Function May Not Influence Outcomes and Survival After Left Ventricular Assist Device Implantation

We investigated changes in estimated glomerular filtration rate (eGFR) after left ventricular assist device (LVAD) implant and the impact on long-term outcomes. A retrospective analysis was conducted for 255 patients with LVADs, divided into 2 groups based on preimplant eGFR (<60 or >60 mL/min/1.73 m2) and into 6 grades (grade 1, >90 mL/min/1.73 m2 normal; grade 2, 60-89 mild dysfunction; grade 3, 45-59 moderate; grade 4, 30-44 moderate to severe; grade 5, 15-29 severe; or grade 6, <15 kidney failure). Changes in eGFR and the impact on long-term outcome and survival were analyzed. One-month postimplant eGFR of the total cohort increased from a baseline of 75.19 ± 34.35 to 118.97 ± 67.62 mL/min/1.73 m2(P < .001). eGRF 4 years postimplant was higher than baseline but not significantly (P= .48). Patients with a preimplant eGFR > 60 followed the same pattern as the entire cohort. The preimplant eGFR < 60 group had a significant increase at 1 month (P < .001), eGFR remained significantly higher than baseline 4 years postimplant (P= .032), and there was a sustained transition to improved distribution of renal function grade after LVAD implant. Post-LVAD implant survival at 1, 3, and 5 years for baseline eGFR > 60 was 76%, 54%, and 48% and for eGFR < 60 was 71%, 60%, and 48%, respectively (P= .92). Patients with a low preimplant eGFR derive benefit from LVAD therapy, with eGFR remaining elevated above preimplant levels. Preimplant renal dysfunction did not impact negatively on long-term morbidity and mortality.

Impact of Acute Kidney Injury and Baseline Renal Impairment on Prognosis Among Patients Undergoing Percutaneous Coronary Intervention.

Both chronic kidney disease (CKD) and acute kidney injury (AKI) are associated with adverse consequences among patients undergoing percutaneous coronary intervention (PCI). However, it remains undetermined whether the impact of CKD and post-PCI AKI are similar. We aimed to discriminate between the impact of CKD and post-PCI AKI on short- and long-term outcomes. This retrospective cohort study included 1,100 patients undergoing PCI at a tertiary hospital. Based on baseline kidney function, patients were categorized as having preserved or impaired renal function, defining as an estimated glomerular filtration rate (eGFR) of ≥ and < 45 ml/min/1.73 m2, respectively. Post-PCI AKI was defined as ≥ 100% relative increase between baseline and post-procedural serum creatinine. Post-PCI AKI was associated with an increased risk of 90-day mortality [odds ratio (OR): 22.03, 95% confidence interval (CI): 10.36-46.88], long-term mortality [hazard ratio (HR): 6.63, 95% CI: 4.31-10.20], and composite endpoint of future end-stage renal disease (ESRD) and death (HR: 6.19, 95% CI: 4.06-9.42). Impaired kidney function at baseline was associated with an increased risk of future ESRD and composite endpoint of ESRD and death (for every 10 unit increase in eGFR, HR: 0.25, 95% CI: 0.14-0.43, and HR: 0.89, 95% CI: 0.82-0.97, respectively). The impact of post-PCI AKI outweighed that of impaired baseline renal function on short- and long-term prognosis. Patients with impaired baseline renal function who developed AKI following PCI had the worst prognosis. Both post-PCI AKI and CKD were associated with a poor prognosis. Post-PCI AKI was more important than baseline renal function to predict long-term mortality and composite outcomes. The systemic pathophysiologic change accompanying AKI, rather than renal function per se, may play a crucial role.

Daratumumab in Patients with Multiple Myeloma and Renal Impairment - Real-World Data from a Single-Center Institution

Background: Renal impairment is a frequent complication of multiple myeloma (MM) associated with poor prognosis and decreased overall survival; and can complicate drug dosing, limit treatment options and lead to a higher incidence of adverse events. Daratumumab is an anti-CD38 monoclonal antibody indicated for the treatment of patients with MM which does not require dose modification in the setting of renal impairment. Real-world data regarding its efficacy in patients with renal impairment and the rate of renal response are lacking. Methods: We performed a retrospective, single-center analysis of patients with relapsed/refractory MM treated with daratumumab as monotherapy or in combination with novel agents. Patients were grouped by renal function as calculated by their eGFR using the MDRD equation: &lt;30, 30-59, &gt;=60 mL/min/1.73m2. Renal response was defined as an eGFR &gt;= 60 in two consecutive visits for patients with baseline renal impairment. Results: We identified 91 patients who started treatment with daratumumab between 2015-06-11 and 2018-08-16. The median age was 69 years old (range 40-93) and 25% were over the age of 75; 49 patients (54%) were female. Six patients (9%) were Hispanic, 16 (20%) were African American and 57 (71%) were Caucasian. High-risk cytogenetics were present in 58% of patients; defined as the presence of a complex karyotype, 1q gain, t(4;14), t(14;16), t(14;20) or del17p. Patients underwent a median of 5 prior lines of therapy (range 1-13), 45% had received an autologous stem cell transplant, 91% had been exposed to an immunomodulatory agent, 96% to a proteasome inhibitor, and 89% to both. Upon initial treatment, 53 patients (58%) had an eGFR &gt;=60 mL/min/1.73m2, while 27 (30%) and 11 (12%) patients had an eGFR of 30-59 and &lt;30 mL/min/1.73m2, respectively. The overall response rate (ORR) was 81% with a very good partial response (VGPR) or better of 47% and an unconfirmed complete response rate (uCR) of 23%. The median progression-free survival (mPFS) was 17.5 months while median overall survival (mOS) was not reached. There was no difference in mPFS or mOS between renal function groups. Of the 38 patients with baseline renal impairment (eGFR &lt;60 mL/min/1.73m2), 11 patients (29%) achieved a renal response, however, none of these patients had severe renal impairment. When compared to patients with chronic renal impairment, those with acute renal impairment were more likely to achieve a renal response (80% vs 21%, p=0.02). No significant difference in mPFS or mOS was observed by renal response (mPFS: 25.7m vs 17.5m, p=0.2; mOS: NR vs NR, p=0.8). Each renal function group was well balanced for the above parameters, including adverse events of interest and concurrent myeloma therapy as shown in the table, except where indicated (*). Discussion: The results of this analysis provide comparable efficacy - independent of the degree of baseline renal impairment - to the results seen in clinical trials of combination therapy with daratumumab. Furthermore, the high renal response rate (29%) seen, as compared to the one in the subgroup analysis of ENDEAVOR (15%), highlights the utility of daratumumab in reversing renal end-organ damage in patients with relapsed/refractory MM without an increase in adverse events compared to patients with preserved renal function. These results suggest that daratumumab may be able to abrogate the adverse prognostic factor that impaired baseline renal function portends. A limitation of this study is its retrospective nature, the confounding effect of concurrent myeloma therapy and the small number of patients included with renal impairment. Table Disclosures Coleman: Merck: Research Funding; Pharmacyclics: Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding.

Differences in clinico-pathological characteristics and outcomes between proteinase 3-ANCA positivity and myeloperoxidase-ANCA positivity in lupus nephritis

Owing to the low prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in lupus nephritis (LN), there is no study about the differences between proteinase 3 (PR3)-ANCA positivity and myeloperoxidase (MPO)-ANCA positivity in LN until now. Here we perform a retrospective study to determine whether there are differences in clinic-pathological characteristics and renal outcomes between PR3-ANCA-positive LN patients and MPO-ANCA-positive LN patients. A total of 26 (27.4%) PR3-ANCA-positive LN patients and 69 (72.6%) MPO-ANCA-positive LN patients (p < 0.001) were eligible for this study. Compared with PR3-ANCA-positive LN patients, MPO-ANCA-positive LN patients had significantly higher levels of serum creatinine (109.6 µmol/l vs. 74.3 µmol/l, p = 0.02), lower titers of antinuclear antibodies (ANA) (128 vs. 256, p = 0.01), and higher serum concentrations of C3 and C4 (0.54 g/l vs. 0.36 g/l, p = 0.002; 0.12 g/l vs. 0.06 g/l, p < 0.001; respectively). Furthermore, the MPO-ANCA-positive group had higher scores for chronicity index (p = 0.007), including interstitial fibrosis (p = 0.001) and tubular atrophy (p = 0.03) on biopsy specimens. The renal survival rates for MPO-ANCA-positive LN patients were 94.1% at 1 year, 83.2% at 5 years and 79.6% at 10 years; these values were worse when compared with those of the PR3-ANCA-positive group, which were 100%, 100% and 100%, respectively. MPO-ANCA-positive LN patients had more severely impaired baseline renal function and less active lupus serology. More severely chronic pathological changes, including interstitial fibrosis and tubular atrophy on renal specimens, occurred in MPO-ANCA-positive LN patients. We found that MPO-ANCA-positive LN patients had worse renal outcomes.

Renal relapse in antineutrophil cytoplasmic autoantibody-associated vasculitis: unpredictable, but predictive of renal outcome.

To determine predictors of renal relapse and end-stage renal failure (ESRF) in patients with ANCA-associated vasculitis. Data from four European Vasculitis Society randomized controlled trials, conducted roughly simultaneously between 15 March 1995 and 30 September 2002, was pooled to determine predictors of long-term renal outcome. The respective trial inclusion criteria covered the entire spectrum of disease severity. Baseline predictors of time to first renal relapse and time to ESRF were assessed by competing events analysis and Cox proportional hazards regression. The effect of renal relapse on time to ESRF was assessed by adding renal relapses to the competing events analysis as a time-varying covariate. The number of patients participating was 535; mean serum creatinine (±s.d.) at entry was 341 ± 321 µmol/l and 19.7% developed ESRF. One or more renal relapse(s) was experienced by 101 patients. Multivariable regression analysis demonstrated that, in addition to impaired baseline renal function, developing ⩾1 renal relapse was an independent risk factor for ESRF (subhazard ratio 9; 95% CI 4, 19; P < 0.001). No predictive factors for renal relapse were found. In addition to baseline renal function, the occurrence of renal relapses is an important determinant of ESRF in patients with ANCA-associated vasculitis. We did not find any clinical predictors for renal relapse itself, including disease activity elsewhere. In light of the silent nature of renal relapse in ANCA-associated vasculitis, we stress the need for long-term vigilant monitoring for early signs of renal relapse and propose performing 3-monthly urinalysis. This will enable timely treatment and help further improve renal outcome.

The Inverse Association between the Baseline Renal Function and Overall Survival in Patients with Metastatic Renal Cell Carcinoma Treated with Molecular-Targeted Agents

Background: The objective of this study was to investigate the prognostic significance of the baseline renal function in metastatic renal cell carcinoma (mRCC) patients treated with molecular-targeted agents. Patients and Methods: This study included 408 consecutive mRCC patients receiving molecular-targeted therapy, consisting of 124 patients in group A and 284 patients in group B who had baseline estimated glomerular filtration rates ≥ 60 ml/min/1.73 m² and < 60 ml/min/1.73 m², respectively. Results: Compared with group A, group B was significantly less likely to have poor prognostic factors, such as a high proportion of patients without nephrectomy. The median overall survivals (OSs) after the initiation of targeted therapy in groups A and B were 21.4 and 35.8 months, respectively, and there was a significant difference in the OS between the 2 groups. However, multivariate analysis showed a lack of independent impact of the baseline renal function on the OS. Furthermore, when patients without a nephrectomy were excluded, no significant difference was noted in the OS between the 2 groups. Conclusion: These findings suggested that there was no adverse impact of an unfavorable baseline renal function on the efficacy of targeted agents against mRCC. Thus, molecular-targeted therapy should not be avoided in mRCC patients with an impaired baseline renal function.

Prognostic implication of post-MitraClip vena contracta area in heart failure patients with functional mitral regurgitation.

Significant functional mitral regurgitation (FMR) in elderly heart failure patients is increasingly being treated by MitraClip implantation. We sought to assess the prognostic implications of the intraprocedural assessment of vena contracta area (VCA) after MitraClip therapy in such patients. MitraClip therapy with intraprocedural assessment of VCA was performed in 97 heart failure patients (74±10 years; 66 men; left ventricular ejection fraction [LVEF] 31±12%; 93 patients in New York Heart Association [NYHA] functional Class III [n=59] or IV [n=34]; 86 patients with FMR severity 3+ [n=65] or 4+ [n=21]). Ninety-one patients (94%) were discharged with FMR severity ≤2+. During a median follow-up of 13.4 (interquartile range 4.6-21.1) months, 32 patients died. Multivariable Cox regression identified increasing age (HR [95% confidence interval]=1.05 [1.00-1.09], p=0.0395), a glomerular filtration rate <50 ml/min/1.73 m² (HR=2.7 [1.3-5.7], p=0.0115), and post-MitraClip VCA >25 mm² (HR=4.5 [2.1-9.5], p=0.0001) as independent predictors of mortality. In heart failure patients with FMR undergoing MitraClip therapy, increasing age, impaired baseline renal function and post-MitraClip VCA >25 mm² are strongly associated with mortality. Post-MitraClip VCA may be used as intraprocedural guidance with respect to patients' long-term outcome.

Serum Potassium Levels and Outcome in Acute Heart Failure (Data from the PROTECT and COACH Trials)

Serum potassium is routinely measured at admission for acute heart failure (AHF), but information on association with clinical variables and prognosis is limited. Potassium measurements at admission were available in 1,867 patients with AHF in the original cohort of 2,033 patients included in the Patients Hospitalized with acute heart failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion trial. Patients were grouped according to low potassium (<3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (>5.0 mEq/l) levels. Results were verified in a validation cohort of 1,023 patients. Mean age of patients was 71 ± 11years, and 66% were men. Low potassium was present in 115 patients (6%), normal potassium in 1,576 (84%), and high potassium in 176 (9%). Potassium levels increased during hospitalization (0.18 ± 0.69 mEq/l). Patients with high potassium more often used angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists before admission, had impaired baseline renal function and a better diuretic response (p= 0.005), independent of mineralocorticoid receptor antagonist usage. During 180-day follow-up, a total of 330 patients (18%) died. Potassium levels at admission showed a univariate linear association with mortality (hazard ratio [log] 2.36, 95% confidence interval 1.07 to 5.23; p= 0.034) but not after multivariate adjustment. Changes of potassium levels during hospitalization or potassium levels at discharge were not associated with outcome after multivariate analysis. Results in the validation cohort were similar to the index cohort. In conclusion, high potassium levels at admission are associated with an impaired renal function but a better diuretic response. Changes in potassium levels are common, and overall levels increase during hospitalization. In conclusion, potassium levels at admission or its change during hospitalization are not associated with mortality after multivariate adjustment.

809P - Inverse association between baseline renal function and overall survival in patients with metastatic renal cell carcinoma who were treated with molecular-targeted agents

Renal toxicity is regarded as one of the most frequently observed adverse events in metastatic renal cell carcinoma (mRCC) patients, irrespective of the type of targeted agent introduced. The objective of this study was to investigate the prognostic significance of the baseline renal function in mRCC patients treated with molecular-targeted agents. This study included a total of 408 consecutive mRCC patients receiving molecular-targeted therapy, consisting of 124 (group A) and 284 (group B) who had baseline estimated glomerular filtration rates ≥ 60 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively. Compared with group A, group B was significantly less likely to have poor prognostic factors, such as a high proportion of patients without nephrectomy, unfavorable risk classified by the Memorial Sloan Kettering Cancer Center or Heng's system, high C-reactive protein level, and high incidence of lymph node, bone or liver metastasis. The median overall survivals (OSs) after the initiation of targeted therapy in groups A and B were 21.4 and 35.8 months, respectively, and there was a significant difference in the OS between these two groups; however, multivariate analysis showed the lack of independent impact of the baseline renal function on the OS. Furthermore, when patients without nephrectomy were excluded, no significant difference was noted in the OS between the two groups. There appeared to be an inverse association between the baseline renal function and OS in mRCC patients receiving molecular-targeted therapy, suggesting no adverse impact of an unfavorable baseline renal function on the efficacy of targeted agents against mRCC. Accordingly, molecular-targeted therapy should not be avoided in mRCC patients with an impaired baseline renal function.

Prognostic Implications of Acute Renal Impairment among ST Elevation Myocardial Infarction Patients with Preserved Left Ventricular Function

Background: Only limited data is present regarding the incidence and prognostic implications of acute kidney injury (AKI) in ST elevation myocardial infarction (STEMI) patients with preserved left ventricular (LV) function in the primary percutaneous coronary intervention (PCI) era. Methods: We conducted a retrospective study of 842 consecutive STEMI patients with preserved LV function (ejection fraction ≥50%, assessed by echocardiography) who underwent primary PCI between January 2008 and January 2015. AKI was defined as an increase of ≥0.3 mg/dl in serum creatinine within 48 h following admission. Patients were assessed for all-cause mortality up to 5 years. Results: Fifty-two patients (6.2%) developed AKI. Patients with AKI were older, had impaired baseline renal function, and presented more often with heart failure throughout their hospitalization. Patients with AKI had a higher 5-year all-cause mortality (13.4 vs. 2.4%, p < 0.001). Compared to patients with no AKI, the adjusted hazard ratio for all-cause mortality was 2.64 (95% CI 1.25-5.56, p = 0.01). Conclusions: Among STEMI patients with preserved LV function undergoing primary PCI, AKI is associated with a higher long-term mortality.

Renal Function in Chronic Hepatitis B Patients Treated With Tenofovir Disoproxil Fumarate or Entecavir Monotherapy

Tenofovir (TDF)-associated renal dysfunction has been described in various studies of human immunodeficiency virus-infected patients. Our goal is to examine the incidence and magnitude of decrease in renal function in chronic hepatitis B patients treated with TDF. We performed a case-cohort study of 103 patients on TDF 300 mg and 103 patients unexposed to TDF (Entecavir) at 4 centers, who were matched for age±10 years, sex, and baseline estimated glomerular filtration rate (eGFR) group. Calculation and evaluation of eGFR were performed with both the Cockcroft-Gault formula and the Modification of Diet in Renal Disease formula. The exposed and unexposed populations were well matched with a similar mean age (44±10 y), proportion of male patients (63.1%), and baseline eGFR groups (86.4% unimpaired). There was no significant difference in the proportion of patients reclassified to a more severe renal classification (RMSRC) or in the proportion of patients with decrease in eGFR of ≥20% in those exposed to TDF versus control. The incidence density for RMSRC was 7.4 cases per 100 patient-years in the exposed group compared with 11.5 cases per 100 patient-years in the unexposed group (95% CI, 0.31-1.34). The relative risk of exposed to unexposed was 0.64 (95% CI, 0.31-1.34). On Cox proportional hazard analysis following adjustment for sex, age, baseline diagnosis hypertension, diabetes, impaired baseline renal function, and cirrhosis, TDF was not a predictor for RMSRC or decrease in eGFR≥20%. TDF treatment was not an independent predictor for significant deterioration of renal function. Renal function of chronic hepatitis B patients on antiviral therapy should be monitored, especially in those who are older and/or with mildly impaired renal function.

Risk Factors for Development of Acute Kidney Injury in Patients with Urinary Tract Infection.

Acute kidney injury (AKI) is associated with high morbidity and mortality. Urinary tract infection (UTI) may be associated with sepsis or septic shock, and cause sudden deterioration of renal function. This study investigated the clinical characteristics and change of renal function to identify the risk factors for development of AKI in UTI patients. This retrospective study was conducted in a tertiary referral center. From January 2006 to January 2013, a total of 790 UTI patients necessitating hospital admission were included for final analysis. Their demographic and clinical characteristics and comorbidities were collected and compared. Multivariate logistic regression analysis was performed to evaluate the risk factors for AKI in UTI patients. There were 97 (12.3%) patients developing AKI during hospitalization. Multivariate logistic regression analysis showed that patients with older age (OR 1.02, 95% CI 1.00–1.04, P = 0.04), diabetes mellitus (DM) (OR 2.23, 95% CI 1.35–3.68, P = 0002), upper UTI (OR 2.63, 95% CI 1.53–4.56, P = 0001), afebrile during hospitalization (OR 1.71, 95% CI 1.04–2.83, P = 0036) and lower baseline eGFR [baseline eGFR 45–59 mL/min/1.73 m2 (OR 2.12, 95% CI 1.12–4.04, P = 0.022), baseline eGFR 30-44 mL/min/1.73 m2 (OR 4.44, 95% CI 2.30–8.60 P < 0.001) baseline eGFR < 30 mL/min/1.73 m2 (OR 4.72, 95% CI 2.13–10.45, P <0.001), respectively] were associated with increased risk for development of AKI. were associated with increased risk for development of AKI. Physicians should pay attention to UTI patients at risk of AKI (advancing age, DM, upper UTI, afebrile, and impaired baseline renal function).

Pneumoperitoneum in the Presence of Acute and Chronic Kidney Injury: An Experimental Model in Rats

There is evidence that pneumoperitoneum induces transient changes in renal function in healthy individuals. Its effect on malfunctioning kidneys is not well known. We investigated effects caused by pneumoperitoneum in animals with impaired renal function. Male Wistar rats underwent subtotal (5/6) nephrectomy in 2 sequential steps to induce renal failure. Two and 10 weeks postoperatively rats were classified with acute and chronic kidney injury, respectively. At those time points all rats were exposed to 0, 5 and 8 mm Hg pneumoperitoneum for 60minutes. Changes in creatinine, blood urea nitrogen and creatinine clearance were measured. Histopathological changes and apoptosis were also evaluated in the subgroups. A total of 18 rats with acute and 18 with chronic kidney injury completed the study. Creatinine and blood urea nitrogen did not change after applying pneumoperitoneum in the different pressure subgroups but creatinine clearance significantly decreased in the 5 and 8 mm Hg subgroups in rats withacute and chronic kidney injury. Histopathological findings in the acute kidney injury subgroups that underwent 5 and 8 mm Hg pressure revealed ischemic changes while compensatory hypertrophy was noticed in the chronic injury pressurized subgroups. The apoptotic count was significantly higher in thechronic injury subgroups compared to their acute injury pressurized counterparts. Pneumoperitoneum seems feasible in rats with impaired baseline renal function. Particularly chronic cases should not be considered a contraindication to pneumoperitoneum while in acute cases pneumoperitoneum might be detrimental.

The impact of kidney function on the outcome of metastatic renal cell carcinoma patients treated with vascular endothelial growth factor‐targeted therapy

A study was undertaken to investigate the effect of baseline renal function on treatment outcome in patients treated with vascular endothelial growth factor (VEGF)-targeted therapy for metastatic renal cell carcinoma (mRCC). Retrospective data from 6 North American cancer centers (3 US and 3 Canadian) were pooled to identify patients with mRCC treated with VEGF-targeted therapy. Patient characteristics, response rate, time to treatment failure, and overall survival were collected. The Modification of Diet in Renal Disease formula was used at therapy initiation for calculation of glomerular filtration rate (GFR). Five hundred twenty-nine patients with mRCC who received sunitinib (n = 323), sorafenib (n = 165), or bevacizumab (n = 41) were included in this analysis. Patient characteristics included: 74% male, median age 61 years, and median GFR 60.1 mL/min/1.73 m(2) (range, 6.5-174.2). On univariate analysis, patients with a GFR <60 (n = 262) were more likely to have had a previous nephrectomy (P < .0001) and to be older (P < .0001), but were less likely to have poor prognostic features such as anemia (P = .041), hypercalcemia (P = .008), neutrophilia (P = .039), thrombocytosis (P < .0001), short diagnosis to treatment interval (P = .007), and low Karnofsky performance status (P = .051). GFR <60, when adjusted for poor risk factors, did not have an impact on type of objective response (odds ratio, 1.31; 95% confidence interval [CI], 0.74-2.32; P = .359), time to treatment failure (hazard ratio [HR], 0.97; 95% CI, 0.79-1.19; P = .772), or overall survival (HR, 0.90; 95% CI, 0.69-1.17; P = .439). Renal function at therapy initiation does not adversely affect the efficacy of VEGF-targeted therapy in mRCC. Clinicians should not avoid treating patients with impaired baseline renal function.

Nephrotoxicity of iodixanol versus iopamidol in patients with chronic kidney disease and diabetes mellitus undergoing coronary angiographic procedures

The choice of radiographic contrast media for use in patients at increased risk of contrast-induced nephropathy (CIN) is of ongoing interest. The current study is a prospective, multicenter, randomized, double-blind design comparing the renal effects of the non-ionic, iso-osmolal agent, iodixanol, versus the non-ionic, low-osmolal agent, iopamidol, in 526 subjects with impaired baseline renal function (chronic kidney disease) and diabetes mellitus undergoing diagnostic and/or therapeutic coronary angiographic procedures. The co-primary end points were the peak increase in serum creatinine (SCr) and the incidence of CIN (increase > or =0.5 mg/dL) in SCr from baseline within 3 days of receiving contrast media. In 418 evaluable subjects with complete postcontrast media SCr data, the median peak increase in SCr in the iodixanol arm was 0.10 mg/dL, whereas in the iopamidol arm, the median peak increase was 0.09 mg/dL (P = .13). The overall CIN incidence was 10.5% (11.2% % in the iodixanol arm and 9.8% in the iopamidol arm, P = .7). The volume of contrast media, volume of saline administered, frequency of coronary interventional procedures, and severity of baseline kidney disease and of diabetes mellitus were similar between treatments. In the present study, the overall rate of CIN in patients with chronic kidney disease and DM undergoing coronary angiographic procedures was 10.5%. There was no significant difference between iodixanol and iopamidol in either peak increase in SCr or risk of CIN.

Acute Kidney Injury in the Elderly: Pathogenesis, Diagnosis and Therapy

Elderly patients, especially those with chronic kidney disease, are at least a 3.5-fold higher risk for the development of acute kidney injury (AKI). With aging, renal functional reserve is lower owing to specific cellular changes that affect function. Molecular studies are elucidating these cellular changes and offer the prospect of designing novel therapeutics. The spectrum of AKI in elderly patients is wide but is over-represented by prerenal and postrenal (obstructive) etiologies. This reflects potentially nephrotoxic clinical variables, such as combordid states, impaired baseline renal function, polypharmacy and an increase in high-risk procedures. In this population, the development of AKI can lead to longer hospital stays, higher mortality rates and an increased risk for the development of chronic kidney disease and end-stage renal disease. Careful attention to clinical risk factors, avoidance of nephrotoxic insults and meticulous supportive care for patients who develop AKI is critical in alleviating the burden of this problem.

Suppression of HIV-1 replication by antiretroviral therapy improves renal function in persons with low CD4 cell counts and chronic kidney disease

To examine the association between changes in glomerular filtration rates (GFR) and antiretroviral therapy (ART)-mediated suppression of plasma HIV-1 viremia. : Observational, prospective, multicenter cohort study. ART regimens or treatment strategies in HIV-1-infected subjects were implemented through randomized clinical trials; 1776 ambulatory subjects from these trials also enrolled in this cohort study. The association between suppression of viremia and GFR changes from baseline was examined using the abbreviated Modification of Diet and Renal Disease equation in mixed effects linear models. GFR improvement was associated with ART-mediated suppression of plasma viremia in subjects with both chronic kidney disease stage > or = 2 and low baseline CD4 cell counts (< 200 cells/microl). In this subset, viral suppression (by > 1.0 log10 copies/ml or to < 400 copies/ml) was associated with an average increase in GFR of 9.2 ml/min per 1.73 m(2) from baseline (95% confidence interval, 1.6-16.8; P = 0.02) over a median follow-up of 160 weeks. The magnitude of this association increased in subjects who had greater baseline impairment of renal function, and it did not depend on race or sex. Viral suppression was associated with GFR improvements in those with both low CD4 cell counts and impaired baseline renal function, supporting an independent contribution of HIV-1 replication to chronic renal dysfunction in advanced HIV disease. GFR improvement not associated with viral suppression also was observed in subjects with higher CD4 cell counts.

Partial nephrectomy achieves local tumor control and prevents chronic kidney disease

Over the last 10 years, a rapidly changing clinical landscape has created an optimal environment to expand the use of partial nephrectomy for the treatment of renal cortical tumors. The main factors responsible for the increasing use of partial nephrectomy relate to the appreciation of the diversity of renal cortical tumor histology, the tumor stage and size migration associated with their incidental detection, and the oncological efficacy of partial nephrectomy for tumors of 7 cm or smaller. Evidence has now emerged that radical nephrectomy performed during the treatment of a small renal mass may further reduce an already impaired baseline renal function and place the patient in the realm of chronic kidney disease. Important new information concerning chronic kidney disease, a condition far more prevalent in the aging US population than previously appreciated, and its associated cardiovascular morbidity and mortality, now places maximal renal functional preservation on a par with local tumor control as surgical plans are formulated for the resection of a small renal cortical tumor.