Including Kidney Transplant Recipients Research Articles

Exercise and cognitive function in patients with end-stage kidney disease.

In this review we summarize the research pertaining to the role of exercise in preventing cognitive decline in patients with end-stage kidney disease (ESKD). Impairment in cognitive function, especially in executive function, is common in patients with ESKD, and may worsen with maintenance dialysis as a result of retention of uremic toxins, recurrent cerebral ischemia, and high burden of inactivity. Cognitive impairment may lead to long-term adverse consequences, including dementia and death. Home-based and intradialytic exercise training (ET) are among the nonpharmacologic interventions identified to preserve cognitive function in ESKD. Additionally, cognitive training (CT) is an effective approach recently identified in this population. While short-term benefits of ET and CT on cognitive function were consistently observed in patients undergoing dialysis, more studies are needed to replicate these findings in diverse populations including kidney transplant recipients with long-term follow-up to better understand the health and quality of life consequences of these promising interventions. ET as well as CT are feasible interventions that may preserve or even improve cognitive function for patients with ESKD. Whether these interventions translate to improvements in quality of life and long-term health outcomes, including dementia prevention and better survival, are yet to be determined.

Glucose and Lipid Metabolism Abnormalities among Patients with Autosomal Dominant Polycystic Kidney Disease

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic renal disease with a prevalence of 1:1,000 births and it is the 4th most common cause of dialysis-dependent end-stage renal disease (ESDR). Recent reports suggest an association between APDKD and metabolic derangements, particularly impaired glucose metabolism. Methods: In this cross-sectional study we analyzed data obtained from case records of 189 patients with ADPKD, including kidney transplant recipients, managed in an outpatient department. Results: The mean BMI was 25.4 ± 3.9; 25.25 before and 27.7 after transplan­tation. A fasting glucose level above 100 mg/dL (5.6 mmol/L) was observed in 60 patients (29%) – 27% without transplantation and 41% kidney transplant recipients. Diabetes mellitus was diagnosed in 17 patients (8.9%), including 3 (2.3%) without a history of transplantation and 14 (24.1%) after kidney transplantation (p < 0.01). We observed dyslipidemia in 30% and hyperuricemia in 53% of patients. Conclusion: Demonstrated metabolic abnormalities should be considered in maintenance of ADPKD patients, including kidney transplant recipients.

Screening Coccidioides Serology in Kidney Transplant Recipients

Introduction Southern California is one of the endemic areas of coccidioidomycosis and patients receiving immunosuppression including kidney transplant recipients are at higher risk for dissemination and severe disease. Screening Coccidioides serology should have benefit in asymptomatic immunocompromised patients who live in endemic areas. Objective To evaluate the prevalence of Coccidioides serology and living area by zip code in kidney transplant recipients at UCLA for early detection of coccidioidomycosis. Methods We used data from UCLA Kidney Transplant Program. We examined 2,961 patients who underwent kidney transplantation between January 1, 2007 and December 31, 2016. Coccidioides serology testing by ELISA was done before or within 14 days after kidney transplantation. We used the five-digit zip code for mapping the location of the approximate endemic areas. Patients with incomplete zip code or Coccidioides serology were excluded from this study. Results Prevalence of positive Coccidioides IgG and IgM were 1.37% and 2.95%, respectively. (figure) A total of 116 patients had positive results of either IgG or IgM, or both, among these, 32 (27.59%) had isolated IgG positivity and 77 (66.38%) had isolated IgM positivity. Patients who live in highly endemic areas were more likely to have positive Coccidioides serology. (p<0.01) (table) Almost patients with positive and indeterminate serology results were in suspected, established, or highly endemic area. Patients, who were not from endemic areas, were less likely to have positive test results. Conclusions Screening Coccidioides serology is a useful testing in kidney transplant candidates who live in endemic areas. Clinical correlation and confirmation test should be helpful for laboratory interpretation especially in patients with either isolated IgG or IgM positivity. Future directions would include following patients post-transplant to determine whether prophylaxis is successful in prevention reactivation as well as how serology testing results change over time.

Nonsteroidal Anti-Inflammatory Drugs and Analgesics Use by Kidney Transplant Recipients

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics are the most commonly used drugs and are increasingly available over-the-counter (OTC). In certain groups of patients, including kidney transplant recipients, their use may be complicated by adverse effects or drug interactions. The aim of our study was to assess the causes and frequency of OTC NSAIDs or analgesics use, as well as the awareness of related side effects.Material/MethodsWe enrolled 94 randomly selected kidney transplant recipients, who represented 5% of all kidney transplant recipients at our center. An anonymous survey consisting of 23 multiple-choice questions was administered voluntarily and anonymously.ResultsIn all, 63% of study patients confirmed taking the OTC painkillers; 22% of these patients took these drugs at least several times a week, and 4% took these drugs daily. For 38% of the study kidney transplant recipients, NSAIDs or analgesics were reported to be the only way to manage their pain. In addition, 30% of study patients were unaware of the risks associated with these drugs, despite the fact that 89% of the study patients consider physicians the best source of information.ConclusionsOur study found that 63% of kidney transplant recipients regularly took OTC painkillers and 30% were unaware of the potential adverse effects. This necessitates continuous, ongoing education of kidney transplant recipients about the risks of OTC NSAIDs or analgesics use.

Spironolactone in Post-Transplant Proteinuria: A Safe Alternative Therapy

BackgroundAldosterone is involved in the process of renal allograft fibrosis, clinically manifest by proteinuria and allograft dysfunction, with increased risk for cardiovascular death. The treatment with aldosterone antagonists appears to be effective in controlling proteinuria, with a protective effect on progression of renal fibrosis. MethodsThis retrospective, cohort study included kidney transplant recipients from January 1993 to June 2015. Inclusion criteria were persistent proteinuria >0.5 g/d, longer than 6 months, and spironolactone therapy. ResultsOne hundred forty transplant recipients fulfilled the inclusion criteria and were divided into 3 groups, according to proteinuria levels at the beginning of spironolactone therapy: low (<1 g/24 h), intermediate (1–3 g/24 h), and nephrotic (>3 g/24 h). Groups were comparable in demographic data, with a higher incidence of living related donors in the nephrotic group. In patients with proteinuria ≥1 g/d, we observed a significant reduction in proteinuria after 6 months of therapy that persisted over time. Blood pressure and glomerular filtration rate persisted stable over time. Adverse events were not severe to withdrawal therapy. ConclusionsSpironolactone can be a safe alternative to control post-transplant proteinuria, especially in patients with mild to moderate allograft dysfunction with proteinuria ≥1 g/day.

Benefits and Harms of Osteoporosis Medications in Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis.

Complications of chronic kidney disease (CKD) include weak bones and increased fracture risk. To review the benefits and harms of osteoporosis medications (bisphosphonates, teriparatide, raloxifene, and denosumab) compared with placebo, usual care, or active control in terms of bone mineral density (BMD), fractures, and safety in patients with CKD. PubMed and the Cochrane Central Register of Controlled Trials from December 2006 through December 2016. Paired reviewers independently screened abstracts and full-text articles for English-language, randomized, controlled trials that had at least 6 months of follow-up; evaluated osteoporosis medications among patients with CKD; and reported on BMD, fractures, or safety (mortality and adverse events). Two reviewers serially abstracted data and independently assessed risk of bias and graded the strength of evidence (SOE). There were 13 trials (n= 9850) that included kidney transplant recipients (6 trials), patients who had stage 3 to 5 CKD or were receiving dialysis (3 trials), or postmenopausal women with CKD (4 trials). Evidence showed that bisphosphonates may slow loss of BMD among transplant recipients (moderate SOE), but their effects on fractures and safety in transplant recipients and others with CKD are unclear. Raloxifene may prevent vertebral fractures but may not improve BMD (low SOE). Effects of teriparatide and denosumab on BMD and fractures are unclear (very low SOE), and these medications may increase risk for some safety outcomes. Unclear rigor of evidence, possible reporting biases, and scant evidence among patients with stage 3 to 5 CKD. Effects of osteoporosis medications on BMD, fracture risk, and safety among patients with CKD are not clearly established. Kidney Disease: Improving Global Outcomes.

Adiponectin, leptin, nitric oxide, and C-reactive protein levels in kidney transplant recipients: comparison with the hemodialysis and chronic renal failure

Background: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with chronic kidney disease (CKD) including kidney transplant recipients (KTR). Secondary lipid metabolism disorders, endothelial dysfunction, and inflammation enhance the risk of CVD development in these patients. The aim of the present study was to investigate the lipid profile, adiponectin, leptin, nitric oxide (NO), and high sensitivity C-reactive protein (hs-CRP) levels in KTR and to compare these parameters with those of the patients with chronic renal failure (CRF), hemodialysis (HD) patients, and healthy controls.Methods: Serum adiponectin and leptin levels were measured by radioimmunoassay; hs-CRP was determined immunoturbidimetrically. Determination of NO was based on the Griess reaction.Results: Compared with the control group, serum NO and adiponectin levels were significantly higher in the KTR, CRF, and HD groups; hs-CRP levels were significantly higher in the KTR and HD groups; leptin levels were significantly higher in the KTR. In addition, serum NO level was significantly higher in the KTR compared to CRF cases. Adiponectin correlated positively with high density lipoprotein-cholesterol in the control and patient groups. A positive correlation was observed between hs-CRP and NO in the KTR and the patients with CRF. Serum adiponectin levels were inversely correlated with hs-CRP and leptin in the HD group.Conclusion: KTR suffer from inflammation and accompanying changes in levels of adipocytokines and NO which contribute to the increased risk of CVD in these patients.

Persistent Infectious Diarrhea as a Risk Factor for Deterioration of Renal Function in Kidney Transplant Recipients

Background: Gastrointestinal complications are common in kidney transplant recipients. Severe diarrhea might result in graft dysfunction or rejection if being ignored. The study aim was to describe the relationship between kidney allograft function and diarrhea, and to determine how diarrhea is influenced by various immunosuppressive regimens at a single center in Taiwan.Methods: This was a retrospective and comparative study. We included kidney transplant recipients who suffered from persistent diarrhea between January 2009 and August 2015. Survival and regression analyses and sub-analyses of creatinine levels over different diarrhea periods were performed.Results: We eventually collected 62 patients for analyses, including 16 with infectious diarrhea and 46 with non-infectious diarrhea. At 3rd year post transplantation, patients with infectious diarrhea demonstrated a significantly lower cumulative renal function rate (56.3% vs. 84.7%, p&lt;0.05). No significant differences were found between recipients receiving different immunosuppressive regimens in terms of renal function. However, recipients receiving mammalian target of rapamycin (mTOR) inhibitor and mycophenolate mofetil (MMF) tended to show a slower rate for deterioration of renal function.Conclusion: In this study, infectious diarrhea, especially when persisting for more than 10.5 days, does significant damages to renal function and predicts for deterioration of renal function. Besides, regimen of mTOR inhibitor and MMF showed a trend toward reducing incidence of deterioration of renal function. Better understanding of the diarrhea etiologies to provide timely treatment for this illness and appropriate choice of immunosuppressive regimen might help maintain renal function for kidney transplant recipients.

Interventions for preventing thrombosis in solid organ transplant recipients

Interventions for preventing thrombosis in solid organ transplant recipients

Clostridium difficile infection among kidney transplant recipients: frequency, clinical presentation, and outcome.

The objective of this study was to evaluate the frequency of Clostridium Difficile Infection (CDI) among kidney transplant recipients and describe the clinical picture in correlation with the presence of certain risk factors. We included kidney transplant recipients with a functioning graft, who were admitted during the period 1/2012-12/2013, and patients with ESRD who were admitted to undergo Kidney Transplantation (KTx) from a deceased or a living donor in the same period. Patients were screened following clinical indication of gastrointestinal infection. CDI diagnosis was based on a positive stool sample for CD toxins and stool culture. Within the period 2012-2013, we recorded 24 cases of CDI in 19 patients, accounting for a frequency of 5.4% of CDI in our population. In addition to diarrhea, 63.15% ofthe patients presented with fever, 31.25% with anorexia, while abdominal pain was a rare symptom (0.53%). None of the patients had ileus, bowel obstruction or megacolon. Fourteen patients (73.7%) had a history of recent exposure (15days) to antimicrobial agents prior to the evolution of CDI symptoms. A relapse of the CDI infection was identified in five cases. CDI infection is a significant factor of morbidity in patients with KTx and should be considered in the clinical setting of diarrhea, even in cases with no exposure to antibiotic agents.

Switch From Existing Antivirals to Brincidofovir Leads to Improving Renal Function.

Introduction: Cidofovir (CDV) and foscarnet (FOS) have been associated with nephrotoxicity, precluding use in renally impaired patients and shortening treatment in others. Brincidofovir (BCV; CMX001), in Phase 3 development (SUPPRESS Trial) for prevention of CMV post-hematopoietic cell transplant (HCT), is a nucleotide analogue with broad-spectrum double-stranded DNA (dsDNA) antiviral activity and a favorable safety profile. Methods: Study 350 provided expanded access to BCV for life-threatening dsDNA infections. Most subjects were HCT (72%) or solid organ transplant (16%) recipients, and 25% were enrolled due to concerns of nephrotoxicity. Baseline (BL) and on-treatment Glomerular filtration rates (GFR), estimated using the MDRD4 (adults) and Schwartz (children) formulas, were evaluated in subjects with prior CDV +/- FOS and no concomitant CDV or FOS use, regardless of indication and other nephrotoxic agent use. Results: Median BL GFR for 37 subjects with prior but no concomitant CDV use was 87 mL/min. Thirty-two (86%) subjects had a maximum GFR>BL during treatment, and had a median of 6 weeks of BCV, compared to 2 weeks for those subjects without GFR improvement. For subjects with BL GFR<60mL/min, 13/14 had max GFR>BL (8/13 had >20mL/min increase); 10/14 subjects had last on-treatment GFR>BL (7/10 had >20mL/min increase). For subjects with BL GFR<30mL/min, 6/6 had max GFR>BL (4/6 had >20mL/min increase); 5/6 had last GFR>BL (4/5 had increase >20mL/min). Similar analyses were performed on 66 subjects with prior but no concomitant CDV and/or FOS use. Fifty-five (83%) subjects had a max GFR>BL. Of these, increases from BL >20mL/min were seen in 53% subjects with BL GFR<60mL/min and 71% with BL GFR<30mL/min. Conclusions: These data suggest BCV has no negative impact on renal function and may allow recovery of renal function when sufficient time elapses after discontinuation of the contributing antiviral. This supports continued investigation of brincidofovir as a potential treatment option for subjects with or at risk for dsDNA virus infections and at high risk for renal impairment, including kidney transplant recipients. DISCLOSURE:Morrison, M.: Employee, Chimerix, Inc. Brundage, T.: Employee, Chimerix, Inc. Mommeja-Marin, H.: Employee, Chimerix, Inc.

Hispanic/Latino concerns about living kidney donation: a focus group study.

Given the shortage of kidneys for transplant, living kidney donation (LKD) is increasingly used to expand the organ donor pool. Although Hispanics/Latinos need disproportionately more kidney transplants, they receive a smaller proportion of living donor kidney transplants than other ethnic/racial groups. To assess Hispanics' awareness, perceptions, misconceptions, cultural beliefs, and values about and barriers to LKD. Nine focus groups were conducted with 76 adult Hispanics in Chicago, Illinois, between January and March 2012. Focus groups included kidney transplant recipients, living kidney donors, dialysis patients, and the general Hispanic public. Several themes emerged as perceived barriers to LKD. Many participants identified knowledge deficits about LKD, expressing uncertainty about the differences between LKD and deceased donation, and whether kidney disease simultaneously afflicts both kidneys. Many believed that donors experience dramatically shorter life expectancies, are unable to have children, and are more susceptible to kidney disease after donating. Recipients and donors reported that family members were involved in discussions about the donor's decision to donate, with some family members discouraging donation. Financial barriers cited included fear of becoming unable to work, losing one's job, or being unable to pay household bills while recovering. Participants also identified logistic barriers for undocumented immigrants (eg, the inability to obtain government insurance for transplant candidates and uncertainty about their eligibility to donate). Donors desired information about optimizing self-care to promote their remaining kidney's health. Culturally competent interventions are needed to redress Hispanics' knowledge deficits and misconceptions and reduce LKD disparities among Hispanics.

Diabetic nephropathy: changes after diabetes surgery?

Obesity, as a central piece inside metabolic syndrome, is associated with early chronic kidney disease (CKD). In addition, several observational, cross sectional, and longitudinal studies have demonstrated that obesity is as an independent risk factor for the onset, aggravated course, and poor outcomes of CKD including diabetic nephropathy. This implies that when obesity is reversed, many CKD risk factors and CKD itself could be favorably influenced. So all measures aimed at weight loss are recommended to minimize risks from obesity-related conditions and generate improvements in the metabolic profile. Recent evidence shows that bariatric surgery (BS) can revert or improve proteinuria and CKD in morbidly obese patients. The present review is aimed to provide the evidence regarding the beneficial effects of weight loss after BS in different stages of CKD including kidney transplant recipients, with an special focus on the beneficial effect in reducing or improving proteinuria and renal failure. Furthermore, this updated systematic review of the literature analyzes potential adverse effects that BS could induce not only on renal function but also on morbidity and mortality risk in perioperative and postoperative period. Results from the different case reports, meta analysis as well as systematic review of clinical trials show that obesity treatment by way of lifestyle changes, pharmacotherapies and BS can reduce proteinuria and help to prevent loss of renal function. Also BS may reduce complications, and allow obese patients with end-stage renal disease to undergo kidney transplantation with good results.

Concordance of Estimated Glomerular Filtration Rates Using Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology in Renal Transplant Recipients

IntroductionVarious equations have been used to estimate the glomerular filtration rate (GFR) in renal patients, including kidney transplant recipients. Controversy exists concerning which equation is more precise to determine kidney failure. AimThe aim of this study was to analyze the concordance (bias, variability, and exactness) of GFR estimated by the Modification of Diet in Renal Disease (MDRD4) and the Chronic Kidney Disease Epidemiology (CKD-EPI) equations using the Cockcroft-Gault (CG) method as the reference. Material and MethodsThis observational, cross-sectional study included 153 clinically stable patients who underwent kidney transplantation between 2007 and 2009. The GFR was estimated at 12 months after the transplantation using the MDRD and CKP-EPI formula, using CG as the reference. ResultsThe mean GFR for the various methods was as follows: CG = 65.6 ± 23.3 mL/min/1.73 m2, MDRD4 = 54.9 ± 19.3 mL/min/1.73 m2, and CKD-EPI = 55.8 ± 19.6 mL/min/1.73 m2. Good correlations were found between CG-MDRD4 (r = 0.84; P < .001), CG-CKD-EPI (r = 0.87; P < .001), and MDRD4-CKD-EPI (r = 0.98; P < .001). The analysis of concordance detected a bias (normal difference) of −10.6 ± 12.7 versus −9.8 ± 11.3 mL/min/1.73 m2 (P = .006), a variability (percent difference) of 14.5 ± 15.4% versus 13.6 ± 14.5% (P = .031), and an exactness (P30) of 81.7% versus 86.9% (P < .001) of CG-MDRD4 versus CG-CKD-EPI, respectively. For a GFR >60 mL/min/1.73 m2 the exactness was 75.3% versus 83.5% (P < .001) for CG-MDRD4 versus CG-CKD-EPI, and for a GFR ≤60 mL/min/1.73 m2 it was 89.7% versus 91.2% (P < .001). ConclusionsIn our population the CKD-EPI method most approached the CG values, particularly when the GFR was >60 mL/min/1.73 m2.

Cognitive Dysfunction and Depression in Adult Kidney Transplant Recipients: Baseline Findings from the FAVORIT Ancillary Cognitive Trial (FACT)

Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment, and depression are all common in individuals with kidney disease, including kidney transplant recipients. Accordingly, we assessed the prevalence of cognitive impairment and depressive symptoms in transplant recipients and their association with kidney function, plasma total homocysteine, and B-vitamin concentrations. Cross-sectional analysis of baseline data from the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) Ancillary Cognitive Trial (FACT), which included 183 participants in FAVORIT who underwent detailed neuropsychological assessment before the study intervention. The mean age was 54.0 ± 9.5 years (range: 7 to 386 months). Men comprised 55.2% of the cohort, and the mean time between the current transplant and cognitive testing was 7.0 ± 5.8 years. Twenty-four percent of participants reported neurological or psychiatric complaints, and 30% exhibited symptoms of mild to severe depression. Testing revealed evidence of significant and selective deficits in this population: 33% performed more than 1 standard deviation (SD) below normed means on a memory test, 58% fell lower than 1 SD below the norms on a test of attention and mental processing speed, and 33% to 42% fell lower than 1 SD below the norms on several tests of executive function. Lower estimated glomerular filtration rate and lower folate were associated with poorer performance on tests of memory and executive function. These observations confirm previous reports of mood and cognitive impairments in adult kidney transplant recipients. Further research is needed to determine the benefit of B-vitamin supplementation and other interventions in this patient population.

Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases

Nocardiosis is a rare but life-threatening opportunistic infection, especially in immune compromised patients, including kidney transplant recipients. Primary pulmonary infection is the most common clinical pattern, and can easily result in disseminated Nocardia infection if treatment therapy is not adequate at the beginning. In this article, we report a new case of disseminated nocardiosis (lungs, skin, and pericardium) after renal allograft transplantation. We also review the English literature published from 1980 to 2010 and analyze the clinical characteristics of nocardiosis in kidney transplant recipients.

Diagnosis of kidney damage using novel acute kidney injury biomarkers: assessment of kidney function alone is insufficient

Acute kidney injury (AKI) is a syndrome that is associated with a major burden of morbidity and mortality in a variety of high risk patient populations, many of them cared for by intensivists. Following renal transplantation, delayed graft function (DGF) caused by severe acute tubular necrosis (ATN), defined by a requirement for dialysis during the initial post-transplant week, complicates postoperative management, and if prolonged (>14 days), adversely affects allograft survival. Neutrophil gelatinase-associated lipocalin (NGAL) and other novel biomarkers can detect AKI earlier than serum creatinine, and can predict AKI severity in high risk patient populations, including kidney transplant recipients. Hollmen and colleagues now demonstrate that elevated urine NGAL in deceased kidney donors is a significant risk factor for prolonged post-transplant DGF in recipients. These findings have clear implications with regard to potentially improved assessment of deceased donor suitability for potential renal allograft donation. These findings are also consistent with the growing evidence that severe ATN diagnosed by markedly elevated levels of AKI biomarkers is a useful predictor of the requirement for acute renal replacement therapy in AKI patients.

Predictors of Left Ventricular Remodelling in Kidney Transplant Recipents in the First Posttransplant Year

Cardiovascular diseases (CVD) are a major cause of morbidity and leading cause of mortality in almost 50% of patients (pts) with chronic kidney disease (CKD), including kidney transplant recipients. Left ventricular hypertrophy (LVH) is the most common structural alteration and powerful risk factor for cardiovascular complications in the uremic patients. The aim of this study is to analyze predictors of the left ventricular remodelling in the first year after kidney transplantation based on comparison of echocardiographic findings, which had been done before and twelve months after transplantation. In five years retrospective study, we followed up 30 kidney transplant patients in the first post-transplant year. All patients data - blood pressure, BMI, ECG, blood haemoglobin, serum protein, calcium, phosphorus, product of calcium and phosphorus, the values of parathyroid hormone, serum creatinine and creatinine clearance were recorded just before kidney transplantation and in one month interval after transplantation in the first post-transplant year. Echocardiographic examination was done before transplantation and one year after kidney transplantation. Before transplantation, 33% of patients had normal echocardiographic finding and 67% of patients had echocardiographic signs of left ventricular hypertrophy. After first post-transplant year, 63% of patients showed normal echocardiographic finding of LV, while 37% of patients remained with LV hypertrophy. Diastolic dysfunction of LV until the end of study had been reduced in 40% of pts compared to 70% pts at the beginning of the study. The positive echocardiographic remodelling of LV significantly correlated with rising values of haemoglobin (p<0.05), creatinine clearance (p=0.039) and with the reduction of the serum creatinine values (p=0.047), as well as values of parathyroid hormone (p=0.022). These results confirmed positive relationship between echocardiographic remodelling of left ventricular hypertrophy and elimination uraemia-related risk factors after successful renal transplantation.

Subgroup Analyses in Randomized Controlled Trials: The Need for Risk Stratification in Kidney Transplantation

Although randomized controlled trials (RCT) are the gold standard for establishing causation in clinical research, their aggregated results can be misleading when applied to individual patients. A treatment may be beneficial in some patients, but its harms may outweigh benefits in others. While conventional one-variable-at-a-time subgroup analyses have well-known limitations, multivariable risk-based analyses can help uncover clinically significant heterogeneity in treatment effects that may be otherwise obscured. Trials in kidney transplantation have yielded the finding that a reduction in acute rejection does not translate into a similar benefit in prolonging graft survival and improving graft function. This paradox might be explained by the variation in risk for acute rejection among included kidney transplant recipients varying the likelihood of benefit or harm from intense immunosuppressive regimens. Analyses that stratify patients by their immunological risk may resolve these otherwise puzzling results. Reliable risk models should be developed to investigate benefits and harms in rationally designed risk-based subgroups of patients in existing RCT data sets. These risk strata would need to be validated in future prospective clinical trials examining long-term effects on patient and graft survival. This approach may allow better individualized treatment choices for kidney transplant recipients.

Recovery of Kidney Function After Acute Kidney Injury in the Elderly: A Systematic Review and Meta-analysis

The prevalence of elderly individuals continues to increase over time, as does the incidence of acute kidney injury (AKI). However, it is not known whether age is an important prognostic predictor for renal recovery after an episode of AKI. Systematic review of MEDLINE and EMBASE databases and meta-analysis of pooled data using random-effect models. Adults with AKI, not including kidney transplant recipients. Studies published in English between 2000 and 2007 were eligible for this analysis if they met the following inclusion criteria: (1) clear definition of AKI and recovery of kidney function, (2) assessment of kidney function recovery as the primary or secondary outcome, and (3) participant age reported. We contacted the investigators of studies and requested data for recovery of kidney function by patient age. Patient age of 65 years and older and younger than 65 years. Recovery of kidney function defined as independence from dialysis therapy, decrease in serum creatinine level to less than a defined threshold, or return to baseline kidney function. We obtained data for recovery of kidney function by age from 17 studies of patients with AKI. Overall, 31.3% of surviving elderly patients did not recover kidney function compared with 26% of younger patients (pooled relative risk, 1.28, 95% confidence interval, 1.06 to 1.55; P < 0.05). The increased risk of nonrecovery in the elderly remained greater in several subgroups examined through sensitivity analyses, including those stratified by type of dialysis support, time of assessment of recovery (short versus long term), and definition of renal recovery. There was significant heterogeneity among studies with respect to comorbid factors, definition of AKI, and study design. There is impaired recovery of kidney function after AKI in aged individuals. Future studies should be cognizant of "age" as a potential effect modifier in the prognosis after AKI, and clinical trials should focus on improving outcomes in the elderly cohort.