Design, Setting, Participants, and Measurements: Eight subjects with XLH were given a single oral dose of phosphate, followed the next day by combined treatment with phosphate and cinacalcet. Serum measurements of ionized calcium (Ca), phosphate, creatinine, intact PTH, 1,25(OH)₂D, FGF23, and tubular threshold for phosphate/glomerular filtration rate (TP/GFR) were assessed in response to short-term treatment with phosphate and cinacalcet and compared with long-term administration of phosphate and calcitriol.

Results: Oral phosphate load increased serum phosphate, decreased ionized calcium, and increased PTH. Twenty-four hours later, FGF23 significantly increased and 1,25(OH)₂D decreased. The concomitant administration of phosphate and cinacalcet resulted in further decrease in serum Ca²⁺ but suppression of PTH and greater increase in serum phosphate and TP/GFR. Chronic treatment with phosphate and calcitriol resulted in a smaller increment in serum phosphate and high serum FGF23.

Conclusions: Traditional therapy of XLH with phosphate and calcitriol elevates FGF23 and has the potential to stimulate PTH. Short-term treatment with cinacalcet suppresses PTH, leading to increase in TP/GFR and serum phosphate. Thus, long-term clinical studies are needed to investigate whether cinacalcet may be a useful adjuvant in the treatment of XLH, allowing the use of lower doses of phosphate and calcitriol.

Design, setting, participants, & measurements: In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT® assay were highly correlated (r = 0.99). In a subsequent study, 196 children undergoing CPB were prospectively enrolled and serial urine NGAL measurements obtained by ARCHITECT® assay. The primary outcome was AKI, defined as a ≥50% increase in serum creatinine.

Results: AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death.

Conclusions: Accurate measurements of urine NGAL are obtained using the ARCHITECT® platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.

Design, setting, participants, & measurements: Acute renal failure was defined as a rapid deterioration of glomerular filtration rate, with or without oligoanuria or rapidly progressive renal insufficiency, including acute-on-chronic renal failure. Patients who were younger than 15 yr were considered children, those between 15 and 65 yr adults, and those >65 elderly.

Results: Between 1994 and 2006, data on 14,190 native renal biopsies were collected from 112 renal units in Spain. Of these, 16.1% (2281 biopsies) were diagnosed with acute renal failure. The prevalence of the main clinical syndromes was different in the three age groups: Biopsy-confirmed acute renal failure in children was 5.7%, in adults was 12.5%, and in elderly increased significantly to 32.9%. The prevalence of biopsy-confirmed acute renal failure according to cause was as follows: Vasculitis, 23.3%; acute tubulointerstitial nephritis, 11.3%; and crescentic glomerulonephritis types 1 and 2, 10.1%. The prevalence of the different causes differed significantly according to age group.

Conclusions: The Spanish Registry of Glomerulonephritis provides useful information about renal histopathology in biopsy-confirmed acute renal failure. The prevalence of vasculitis and crescentic glomerulonephritis is high, especially in elderly patients. These data obtained from a national large registry highlight the value of renal biopsy in undetermined acute renal failure.

Design, setting, participants, & measurements: Ten patients with systemic lupus erythematosus, antineutrophil cytoplasmic antibody positivity, and renal biopsy findings of lupus nephritis and antineutrophil cytoplasmic antibody–associated glomerulonephritis were identified. The clinical features, pathologic findings, and outcomes are described.

Results: The cohort consisted of eight women and two men with a mean age of 48.4 yr. Perinuclear antineutrophil cytoplasmic antibody was detected by indirect immunofluorescence in nine patients. Four of the nine patients and the single remaining patient were found to have myeloperoxidase–antineutrophil cytoplasmic antibodies by enzyme-linked immunosorbent assay. Clinical presentation included proteinuria, hematuria, and acute renal insufficiency, with mean creatinine of 7.1 mg/dl. All biopsies exhibited prominent necrosis and crescents with absent or rare subendothelial deposits and were interpreted as lupus nephritis and antineutrophil cytoplasmic antibody–associated glomerulonephritis. All patients received cyclophosphamide and prednisone. Three patients died of infectious complications. Among the remaining seven patients, five achieved a complete or near-complete remission, one had a remission with subsequent relapse, and one had no response to therapy.

Conclusion: Antineutrophil cytoplasmic antibody–associated necrotizing and crescentic glomerulonephritis may occur superimposed on lupus nephritis. In patients with lupus nephritis and biopsy findings of prominent necrosis and crescent formation in the absence of significant endocapillary proliferation or subendothelial deposits, antineutrophil cytoplasmic antibody testing by enzyme-linked immunosorbent assay is recommended.

Design, setting, participants, & measurements: A cross-sectional study was conducted of ambulatory patients without diabetes and with different stages of chronic kidney disease (n = 51), compared with gender- and age-matched healthy subjects. Fasting blood was obtained for measurement of advanced glycation end products and mRNA receptor for advanced glycation end product expression in peripheral blood mononuclear cells. Endothelial reactivity was assessed by the microcirculatory response to local ischemia (postocclusive reactive hyperemia) and local hyperthermia (thermal hyperemia). Sera were pooled and passed through affinity columns to separate advanced glycation end product–rich fractions, which were incubated with human aortic endothelial cells, with or without blockade of receptor for advanced glycation end product, to measure their effect on endothelial nitric oxide synthase.

Results: Glomerular filtration rate correlated with serum advanced glycation end product, mRNA receptor for advanced glycation end product levels, postocclusive reactive hyperemia, and thermal hyperemia. Serum advanced glycation end product correlated with receptor for advanced glycation end product and inversely with postocclusive reactive hyperemia. Advanced glycation end product–rich fractions from chronic kidney disease sera suppressed endothelial nitric oxide synthase expression of human aortic endothelial cells compared with sera from healthy subjects, an effect abrogated by receptor for advanced glycation end product blockade.

Conclusions: This study demonstrates for the first time an association of excess advanced glycation end product burden with increased peripheral blood mononuclear cell mRNA receptor for advanced glycation end product and in vivo endothelial dysfunction in patients with chronic kidney disease. Endothelial dysfunction in chronic kidney disease may be partly mediated by advanced glycation end product–induced inhibition of endothelial nitric oxide synthase through receptor for advanced glycation end product activation.

Design, Setting, Participants, and Measurements: We compared the effects of stent versus angioplasty on primary patency rates in the treatment of stenotic arteriovenous fistulae (AVF) and arteriovenous grafts (AVGs). Moreover, we compared access flow (Qa) and urea reduction ratio (URR) between the two groups as a metric of the effect of stent placement versus angioplasty on dialysis delivery.

Results: Cox regression analysis revealed that the primary assisted AVG patency was significantly longer for the stent group compared with angioplasty, with a median survival of 138 versus 61 d, respectively (aHR = 0.17; 95% confidence interval, 0.07 to 0.39; P < 0.001). The primary AVG patency for stent versus angioplasty was 91% versus 80% at 30 d, 69% versus 24% at 90 d, and 25% versus 3% at 180 d, respectively. The primary assisted AVF patency did not differ significantly between the stent and angioplasty groups. In patients dialyzing via AVF, multiple regression analysis revealed that stent placement was associated with improved after intervention peak Qa, 1627.50 ml/min versus 911.00 ml/min (β = 0.494; P = 0.008), change in Qa from before to after intervention, 643.54 ml/min versus 195.35 ml/min (β = 0.464; P = 0.012), and change in URR from before to after intervention, 5.85% versus 0.733% (β = 0.389; P = 0.039).

Conclusions: Our results suggest that stent placement is associated with improved AVG primary assisted patency and improved AVF blood flow, which may significantly impact on dialysis adequacy.

Design, setting, participants, & measurements: Patients with type 1 diabetes and normoalbuminuria or microalbuminuria were recruited to the Second Joslin Kidney Study. A medical history and measurements of BP, hemoglobin A1c, albumin excretion rate, and serum concentrations of uric acid and cystatin C were obtained. Estimated glomerular filtration rate was measured by a cystatin C–based formula.

Results: We studied 364 patients with normoalbuminuria and 311 patients with microalbuminuria. Mean glomerular filtration rate in these groups was 119 and 99 ml/min, respectively. Mildly or moderately impaired renal function (<90 ml/min) was present in 10% of those with normoalbuminuria and 36% of those with microalbuminuria. In univariate and multivariate analyses, lower glomerular filtration rate was strongly and independently associated with higher serum uric acid and higher urinary albumin excretion rate, older age, and antihypertensive treatment.

Conclusions: Serum uric acid concentration in the high-normal range is associated with impaired renal function in patients with type 1 diabetes. Follow-up studies are needed to confirm that this level of serum uric acid is a risk factor for early renal function decline in type 1 diabetes and to determine whether its reduction would prevent the decline.

Design, setting, participants, & measurements: Eleven centers participated in a guidelines implementation program. All new permanent vascular accesses were included. Patency and functional patency, defined as access survival from creation and from first dialysis use, respectively, were calculated using Kaplan-Meier analysis. Risk factors for primary functional patency loss (intervention-free interval) and secondary failure (abandonment) were determined using regression models.

Results: A total of 491 arteriovenous fistulas were placed in 395 patients. Six-, 12-, and 18-mo secondary patency and functional patency were 75 ± 2.0, 70 ± 2.3, and 67 ± 2.7% and 90 ± 1.9, 88 ± 2.2, and 86 ± 2.7%, respectively. Primary failure rate was 40%. Thrombosis rate was 0.14 per patient-year. Diabetes and arteriovenous fistula surveillance were significantly associated with primary functional patency loss. Preoperative duplex was inversely related to secondary failure. The secondary failure rate per hospital varied from 0 to 39%.

Conclusions: This study showed a marked difference between patency and functional patency, likely to be explained by high primary failure rates. Hemodialysis patients with diabetes can be expected to have reduced primary functional patency rates, but if treated adequately, then arteriovenous fistula functionality can be maintained as long as in patients without diabetes.

Design, setting, participants, & measurements: Peritoneal biopsy specimens from 173 uremic (before peritoneal dialysis) and 80 peritoneal dialysis patients with or without impaired ultrafiltration capacity were evaluated by average peritoneal thickness of submesothelial compact zone measured at five randomly selected points of peritoneum and by lumen/vessel diameter ratio at postcapillary venule.

Results: The average peritoneal thickness was increased in uremic patients and progressively thickened as the duration of peritoneal dialysis prolonged. The lumen/vessel diameter ratio was lower in uremia than normal and progressively decreased as the duration of peritoneal dialysis prolonged. In pre–peritoneal dialysis peritoneum, patients with diabetes showed significant decrease in lumen/vessel diameter ratio compared with patients without diabetes. The average peritoneal thickness was significantly higher in patients with impaired ultrafiltration capacity than in patients with maintained ultrafiltration capacity; however, no significant difference was observed in the postcapillary venule thickness and lumen/vessel diameter ratio between the two groups.

Conclusions: The average peritoneal thickness and lumen/vessel diameter ratio were useful morphologic parameters to quantify the severity of the peritoneal alterations in uremic and peritoneal dialysis patients. Uremia and diabetes had an impact on the pathogenesis of peritoneal sclerosis in pre–peritoneal dialysis peritoneum. Peritoneal dialysis treatment itself had a much stronger impact on the progression of peritoneal sclerosis.

Design, Setting, Participants, and Measurements: To evaluate this, we performed a prospective, observational pilot study of 20 chronic hemodialysis patients assessing the baseline AVP level and trend of AVP with ultrafiltration in patients with a diagnosis of IDH compared with patients without IDH. Ten symptomatic IDH patients and 10 controls were enrolled and matched for age, gender, and dialysis vintage. AVP levels were obtained hourly throughout the dialysis session and during hypotensive episodes.

Results: We observed that IDH patients experienced greater decreases in both systolic and diastolic blood pressure during the dialysis session despite equivalent ultrafiltration in both groups. AVP concentration did not increase in the IDH patients (5.0 ± 1.8) compared with controls (6.4 ± 6.0) (P = 0.5) despite hypotensive events.

Conclusions: This study suggests that symptomatic IDH patients are unable to mount an appropriate increase in AVP secretion in the setting of hypotension. These findings support the possibility of AVP as a mechanism driven therapy for patients with symptomatic IDH.

Design, setting, participants, & measurements: Sustained low-efficiency dialysis was performed at blood and dialysate rates of 250 and 300 ml/min, respectively. The circuit was anticoagulated with 4% sodium citrate (citrate 136, sodium 408 mmol/L) and reversed with CaCl₂. Every 2 h, electrolytes, ionized circuit, and patient calcium were monitored during the first two versions. The second version differed by an increased infusion of CaCl₂ and lower infusion of citrate, both by 10%. The third version measured only laboratory values before and after sustained low-efficiency dialysis.

Results: There were 41 treatments in the first iteration, 42 in the second, and 34 in the final iteration. All versions were titrated to maintain patient ionized calcium of 4.0 to 4.8 mg/dl (1.0 to 1.2 mmol/L) and the circuit ionized calcium between 0.8 and 1.6 mg/dl (0.2 and 0.4 mmol/L). The final protocol infusion was 31 mmol/h citrate and 41 mmol/h elemental calcium, which kept circuit and patient ionized calcium at targets. No unexpected metabolic complications occurred.

Conclusions: Compared with continuous renal replacement therapy, one must increase the calcium infusion because of the more efficient removal of the calcium citrate complex. Safe and effective regional citrate anticoagulation can be performed in 8-h sustained low-efficiency dialysis without metabolic complications with laboratory surveillance only before and after sustained low-efficiency dialysis treatment; however, certain safeguards are mandatory.

Design, setting, participants, & measurements: Plasma conductivity (Cp) and mass balance index were compared for 20 sessions without thiosulfate and 20 sessions with thiosulfate infusion. Subsequently, the dialysate conductivity was set to 13.8 mS/cm during the entire session. Next, dialysate conductivity was set to 14 mS/cm for the first 3 h and to 13 mS/cm for the last hour of thiosulfate infusion (n = 25).

Results: The Cp variation between beginning and end was equal to +0.005 ± 0.13 mS/cm without thiosulfate, +0.24 ± 0.13 mS/cm with thiosulfate, and 14 mS/cm dialysate conductivity (P < 0.001). The decrease in dialysate conductivity at 13.8 mS/cm did not counterbalance the sodium load. The last program adequately compensated the sodium load with a Cp increase of only +0.05 ± 0.14 mS/cm (NS versus without thiosulfate). The total of the dialyzed sodium and the sodium load for this last program was equal to 603 mmol compared with 456 mmol for the sessions without thiosulfate, the difference of 147 mmol being close to the known content of 161 mmol in 25 g of infused thiosulfate.

Conclusions: Thiosulfate infusion requires a decrease of dialysate conductivity of –1 mS/cm during the infusion to counterbalance the added 3.7 g (161 mmol) sodium load.

Design, setting, participants, & objectives: Appointment logs were used to generate a database of all long-term hemodialysis patients at the Dallas Veterans Affairs hospital since August 2001. These patients were then examined in the Veterans Affair's electronic medical record system for gadolinium exposure during magnetic resonance imaging from 2000 through 2007, a period during which gadoteridol was the sole contrast agent used.

Results: A total of 141 patients were identified with 198 gadoteridol exposures. No cases of nephrogenic systemic fibrosis were identified. The observed frequency of nephrogenic systemic fibrosis was compared with the expected frequency (2.4%) using one-way ² and binomial analysis, yielding a P < 0.05, indicating that the result was not explained by chance alone.

Conclusions: It is concluded that the risk for nephrogenic systemic fibrosis with gadoteridol in patients who are on long-term hemodialysis may be lower than with gadodiamide and gadopentetate dimeglumine.

Design, setting, participants, & measurements: A prospective cohort study of an outpatient hemodialysis unit was conducted. Serial surveillance cultures for multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus were collected from patients who were undergoing chronic hemodialysis.

Results: Nineteen (28%) of the 67 enrolled patients were colonized with one or more antimicrobial-resistant bacteria at study enrollment. Eleven (16%), nine (13%), and three (5%) patients were colonized with multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Independent risk factors associated with harboring multidrug-resistant gram-negative bacteria at enrollment were residence in a long-term care facility and antibiotic exposure for ≥7 d in the previous 3 mo. Twenty-two (40%) of 55 patients who had follow-up cultures acquired at least one antimicrobial-resistant bacterium. A total of 20, 15, and 13% of patients acquired multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Antibiotic exposure was the only independent risk factor for multidrug-resistant gram-negative bacteria acquisition. Endogenous multidrug-resistant gram-negative bacteria acquisition was detected among 69% of acquired multidrug-resistant gram-negative bacterial strains.

Conclusions: The prevalence and acquisition of multidrug-resistant gram-negative bacteria surpassed that of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Endogenous acquisition, as opposed to patient-to-patient spread, was the predominant mechanism of acquisition. Residence in a long-term care facility and antibiotic exposure may be important factors promoting the spread of multidrug-resistant gram-negative bacteria among this patient population.

Design, setting, participants, & measurements: This retrospective cohort study linked data on patients aged 12 to 18 yr in 1999 and 2000 from the Centers for Medicare and Medicaid Services’ End Stage Renal Disease Clinical Performance Measures Project with 4-yr hospitalization and mortality records in the United States Renal Data System. Albumin was categorized as <3.5/3.2, ≥3.5/3.2 and <4.0/3.7, and ≥4.0/3.7 g/dl.

Results: Of 675 adolescents, 557 were hospitalized and 50 died. Albumin ≥4.0/3.7 g/dl was associated with male gender, Hispanic ethnicity, and higher hemoglobin level. Those with albumin ≥4.0/3.7 g/dl had fewer deaths per 100 patient-years and fewer hospitalizations per time at risk. In multivariate analysis, patients with albumin ≥4.0/3.7 g/dl had 57% decreased risk for death. Poisson regression showed progressive decrease in hospitalization risk as albumin level increased; however, confidence intervals were similar between albumin ≥4.0/3.7 g/dl and albumin ≥3.5/3.2 and <4.0/3.7 g/dl.

Conclusions: This study demonstrates decreased mortality and hospitalization risk with albumin ≥3.5/3.2 g/dl and suggests that adolescent hemodialysis patients who are able to achieve serum albumin ≥4.0/3.7 g/dl may have the lowest mortality risk.

Design, setting, participants, & measurements: This retrospective cohort study, using data from the Australia and New Zealand Dialysis and Transplant registry, included all patients who were aged 35 to 84 yr and started long-term renal replacement therapy in Australia from 1971 through 2006.

Results: Of 31,654 incident renal replacement therapy patients, 10.2% had analgesic nephropathy. Incidence and prevalence of renal replacement therapy attributed to analgesic nephropathy decreased earlier and faster among younger (age <55 yr) patients. Prevalence of analgesic nephropathy among 75- to 84-yr-old renal replacement therapy patients is still increasing. Compared with control subjects without diabetes, comorbidities (coronary artery, cerebrovascular, peripheral vascular, and chronic lung diseases) were more prevalent among patients with analgesic nephropathy at renal replacement therapy start. All-cause, cardiovascular, infection, and cancer mortality were higher among patients who had analgesic nephropathy and were on renal replacement therapy. For both comorbidities and mortality, the associations were stronger in younger patients.

Conclusions: Trends in renal replacement therapy attributed to analgesic nephropathy differed by age. Patients with analgesic nephropathy have more comorbidities and poorer survival on renal replacement therapy, especially among younger patients.

Design, settings, participants, & measurements: A retrospective cohort of 34,963 Fresenius Medical care dialysis patients from 1996 was assembled. Hemoglobin variability, absolute hemoglobin level, and temporal hemoglobin trend were measured over rolling 6-mo exposure windows. Their association with mortality was estimated using history-adjusted marginal structural analysis that adjusts for time-dependent confounding by applying weights to observations inversely related to the predictability of observed levels of hemoglobin.

Results: In the primary analysis, each g/dl increase in hemoglobin variability was associated with an adjusted hazard ratio (HR) [95% confidence interval (CI)] for all-cause mortality of 1.93 (1.20 to 3.10). Neither higher absolute hemoglobin level nor increasing hemoglobin trend were significantly associated with mortality; adjusted HR (95% CI) 0.85 (0.64 to 1.11) and 0.60 (0.25 to 1.45), respectively.

Conclusions: Marginal structural analysis demonstrates that hemoglobin variability is associated with increased mortality among chronic hemodialysis patients, and that this effect is more pronounced than appreciated using standard statistical techniques that do not take time-dependent confounding into account.

Design, setting, participants, & measurements: Designed as a cross-sectional, epidemiologic study, the Insulin Resistance Atherosclerosis Study was conducted in four centers: San Antonio (Texas), San Luis Valley (Colorado), and Oakland and Los Angeles (California). The Modification of Diet in Renal Disease equation was used to classify individuals without diabetes and with normoalbuminuria (n = 856; age 40 to 69 yr) by the presence or absence of low glomerular filtration rate (<60 ml/min per 1.73 m²). A direct marker of insulin resistance, the insulin sensitivity index, was measured by the frequently sampled intravenous glucose tolerance test.

Results: Low glomerular filtration rate was related to hypertension and the metabolic syndrome. Low glomerular filtration rate was associated with fasting insulin concentration and insulin sensitivity index. Low glomerular filtration rate was also associated with insulin concentration after adjustment for potential determinants of glomerular filtration rate but was not associated with insulin sensitivity index.

Conclusions: Low glomerular filtration rate is associated with increased insulin concentration in individuals without diabetes and with normoalbuminuria. Longitudinal analyses are needed to determine whether insulin concentration (insulin resistance) precedes the deterioration of renal function.

Design, setting, participants, & measurements: A prospective study enrolled 30 adult men with autosomal dominant polycystic kidney disease. Of these 30 patients, 22 agreed to provide a semen sample for analysis, and 28 of 30 agreed to undergo an ultrasound rectal examination. Data obtained from the semen tests and from the ultrasound study were compared.

Results: Cysts in the seminal tract were present in 10 (43.47%) of 28 individuals. Twenty of 22 patients showed abnormal semen parameters, with asthenozoospermia as the most common finding. No correlation between ultrasound findings and sperm abnormalities was observed.

Conclusions: The presence of cysts in the seminal tract is remarkably high (43.47%); however, this finding does not correlate with sperm abnormalities, which are also a frequent finding, especially asthenozoospermia. This semen abnormality is probably related to the abnormal function of polycystins. More attention should be paid to reproductive aspects in the initial evaluation of patients with autosomal dominant polycystic kidney disease before their ability to conceive is further impaired by uremia.

Design, setting, participants, & measurements: Studies were performed on 82 parathyroids of 22 adult white hemodialysis patients undergoing first parathyroidectomy. The type of hyperplasia and the distribution of chief and oxyphil cells, expressed as oxyphil/chief cell ratio, were assessed. Three groups could be studied according to treatment modality: group A consisted of 6 patients who were treated with cinacalcet, intravenous calcitriol, and phosphate binders; group B consisted of 6 patients who were treated with intravenous calcitriol and phosphate binders, and group C consisted of 10 patients who were treated with phosphate binders alone.

Results: Sixty-eight (82.9%) out of 82 glands removed showed nodular hyperplasia. It was more frequent in groups A and B than in group C. A stepwise forward logistic regression model showed that the probability of nodular hyperplasia was higher in patients who were on calcitriol and/or cinacalcet therapy, in female gender and in patients with a higher body mass index. Oxyphil/chief cell ratio also was significantly different among the three groups. Cinacalcet treatment was the only predictor of this ratio.

Conclusions: An association was found between calcitriol and/or cinacalcet therapy and a high prevalence of nodular hyperplasia, and between cinacalcet therapy and high oxyphil/chief cell ratio. The meaning of the observed associations remains uncertain.

Design, setting, participants, & measurements: Definition, classification, and limitations in evaluating epidemiology of native and recurrent glomerulonephritis are discussed. Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis was evaluated using data from various registries, and pathogenesis of individual glomerulonephritis is discussed.

Results: Analysis of data from transplant registries revealed that glomerulonephritis is an important cause of end-stage renal disease in white and pediatric recipients; however, glomerulonephritis as the cause of end-stage renal disease is not characterized well in black recipients, and many of them are perhaps labeled to have hypertensive nephrosclerosis as the cause of renal disease without renal biopsy. A systematic approach toward urinalysis after transplantation and utility of immunofluorescence and electron microscopic examination of renal biopsy tissues will identify the true prevalence of recurrent glomerulonephritis. Data on recurrent glomerulonephritis should be compiled by either using registry analysis or pooling data from multiple centers. This will provide true data on prevalence and outcome and could potentially initiate translational research studies.

Conclusions: The understanding of the pathogenesis of recurrent glomerulonephritis is critical to optimize prevention as well as to treat individual recurrent glomerulonephritis, which can enhance long-term graft survival.

Design, setting, participants, & measurements: A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed.

Results: Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and β blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition.

Conclusions: Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention.

Design, setting, participants, & measurements: The association of acute rejection and new-onset diabetes was determined in the first posttransplantation year with the outcomes of transplant failure from any cause, death-censored graft loss, and death with a functioning graft in 27,707 adult recipients of first kidney-only transplants, with graft survival of at least 1 yr, performed between 1995 and 2002 in the United States.

Results: In multivariate analyses, patients who developed acute rejection or new-onset diabetes had a similar risk for transplant failure from any cause, but the mechanisms of transplant failure were different: Acute rejection was associated with death-censored graft loss but only weakly associated with death with a functioning graft. In contrast new-onset diabetes was not associated with death-censored graft loss but was associated with an increased risk for death with a functioning graft.

Conclusions: Acute rejection and new-onset diabetes have a similar impact on long-term transplant survival but lead to transplant failure through different mechanisms. The mechanisms by which new-onset diabetes leads to transplant failure should be prospectively studied. Targeted therapeutic strategies to minimize the impact of various early posttransplantation complications may lead to improved long-term outcomes.

Design, setting, participants, & measurements: A prospective cohort evaluation of 540 patients were followed for a median of 4.7 yr in an outpatient kidney transplant clinic. Baseline Framingham risk scores were calculated and all cardiovascular outcomes were collected.

Results: Rates per 100 patient-years were 1.79 for cardiac and 0.78 for stroke events. The ratio of observed-to-predicted cardiac events was 1.64-fold higher [95% confidence interval (CI) 1.19 to 2.94] for the cohort, 2.74-fold higher (95% CI 1.70 to 4.24) in patients age 45 to 60 with prior cardiac disease or diabetes mellitus, but not higher in other age subgroups. Stroke was not increased above predicted. Risk scores for cardiac (c = 0.65, P = 0.003) and stroke (c = 0.71, P = 0.004) events were modest predictors. 10-yr event scores for cardiac (9.3 versus 13.5%, P < 0.001) and stroke (7.1 versus 10.0%, P = 0.002) were lower for tacrolimus compared with cyclosporine-treated patients. However observed cardiac events were higher in tacrolimus recipients (2.50, 95% CI 1.09 to 5.90) in an adjusted Cox model.

Conclusions: Although risk scores are only modest predictors, patients with the highest event rates are easily identified. Treating high-risk patients with cardioprotective medications should remain a priority.

Design, setting, participants, & measurements: Leflunomide was used in 21 patients with BK nephropathy. These patients were divided into two groups on the basis of the leflunomide levels achieved: Low-level group (<40 µg/ml) and high-level group (>40 µg/ml).

Results: During 13 mo of follow-up, there was no difference in the rate of serum BK viral clearance between the groups. There were three graft losses in the low-level group and one in the high-level group; however, creatinine levels were higher at the time of starting leflunomide in the low-level group. Leflunomide was also used in six patients with chronic allograft injury. No graft loss was observed during the follow-up period of 16 mo. Treatment with leflunomide seemed to be associated with a new toxicity, hemolysis, seen in four of the 27 patients so treated. Patients with hemolysis had high leflunomide levels (81.4 ± 14 µg/ml) and worsening allograft function. Two patients had histologic evidence of thrombotic microangiopathy, which led to graft loss in one patient.

Conclusions: The clinical correlation between leflunomide levels and outcomes needs to be further refined. This study described a possible association of leflunomide with thrombotic microangiopathy, especially at higher levels.

Design, setting, participants & measurements: Three-day, international, consensus conference. A multidisciplinary stakeholder committee was divided into work groups. Recommendations for clinical practice and for future research were developed by the committee as an iterative process. This procedure consisted of a literature review phase and focus group interactions with presentations to the entire committee.

Results: We first proposed a conceptual framework of disease that describes a series of AKI stages, antecedents and outcomes, and allows a description of research recommendations based on transition between AKI stages. We further proposed methods for testing of the definition and development of research questions to establish the utility of new biomarkers for the diagnosis and staging of AKI and associated illnesses.

Conclusions: Retrospective studies should be conducted to initiate the process of validating the AKIN definition of AKI, followed by comprehensive prospective studies that incorporate sampling for emerging AKI biomarkers.

Design, setting, participants, & measurements: The available literature on this topic and draft consensus recommendations for research studies in this area were developed using a modified Delphi approach and an international multidisciplinary network.

Results: The following questions were most important: What is the "dosage" of renal replacement therapy delivered to patients with stage 3 acute kidney injury? What is the optimal "dosage" of renal replacement therapy to maximize patient and renal survival? Is there a minimal "dosage" of renal replacement therapy required in patients with single-organ failure? Does modality of renal replacement therapy selected have an effect on patient and/or renal survival? In cases of continuous renal replacement therapy, does citrate anticoagulation confer a benefit?

Conclusions: This report summarizes the available evidence and elaborates on the key questions and the methods that should be used so that the goal of standardizing the care of patients with acute kidney injury and improving outcomes can be achieved.

Design, setting, participants, & measurements: This article reports on the research recommendations of an international multidisciplinary committee, assembled to define a research agenda on acute kidney injury epidemiology using a modified three-step Delphi process.

Results: Knowledge of incidence and risk factors is crucial because it drives local and international efforts on detection and treatment. Also, notable differences exist between developing and developed countries: Incidence seems higher in the former, but underreporting compounded by age and gender disparities makes available data unreliable. In developing countries, incidence varies seasonally; incidence peaks cause critical shortages in medical and nursing personnel. Finally, in developing countries, lack of systematic evaluation of the role of falciparum malaria, obstetric mechanisms, and hemolytic uremic syndrome on acute kidney injury hampers efforts to prevent acute kidney injury.

Conclusions: The committee concluded that epidemiologic studies should include (1) prospective out- and inpatient studies that measure incidence of community and hospital acute kidney injury and post–acute kidney injury chronic kidney disease; (2) incidence measurements during seasonal peaks in developing and developed countries; and (3) whenever available, use of reliable existing administrative or institutional databases. Epidemiologic studies using standardized definitions in community and institutional settings in developing and underdeveloped countries are essential first steps to achieving early detection and intervention and improved patient outcomes.

Design, setting, participants, & measurements: A three-step modified Delphi process involving 43 participants representing 19 professional societies, organizations, and multiple stakeholder groups ranging from clinical practice to basic science research was conducted.

Results: Twenty research questions were generated across six focus groups. Overall, research priorities generated from nephrologists and intensivists were similar and highly correlated. The stakeholder groups included members from 15 countries. Results from adult and pediatric groups showed important differences, as did results from developing compared with developed countries; however the priority rankings from the developed and developing countries were significantly correlated. Top research priorities in acute kidney injury include determining optimal timing of renal replacement therapy and improving the understanding of the epidemiology of acute kidney injury around the world.

Conclusions: Research recommendations that are highly consistent across various stakeholder groups and between developed and developing countries have been produced. It is hoped that these recommendations will prove valuable in guiding future clinical and translational research in this area.