International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Diabetes mellitus and blood glucose variability increases the 30-day readmission rate after kidney transplantation.

INTRODUCTION: Inpatient hyperglycemia is an established independent risk factor among several patient cohorts for hospital readmission. This has not been studied after kidney transplantation. Nearly one-third of patients who have undergone a kidney transplant reportedly experience 30-day readmission. METHODS: Data on first-time solitary kidney transplantations were retrieved between September 2015 and December 2018. Information was linked to the electronic health records to determine diagnosis of diabetes mellitus and extract glucometric and insulin therapy data. Univariate logistic regression analysis and the XGBoost algorithm were used to predict 30-day readmission. We report the average performance of the models on the testing set on bootstrapped partitions of the data to ensure statistical significance. RESULTS: The cohort included 1036 patients who received kidney transplantation; 224 (22%) experienced 30-day readmission. The machine learning algorithm was able to predict 30-day readmission with an average area under the receiver operator curve (AUC) of 78% with (76.1%, 79.9%) 95% confidence interval (CI). We observed statistically significant differences in the presence of pretransplant diabetes, inpatient-hyperglycemia, inpatient-hypoglycemia, minimum and maximum glucose values among those with higher 30-day readmission rates. The XGBoost model identified the index admission length of stay, presence of hyper- and hypoglycemia, the recipient and donor body mass index (BMI) values, presence of delayed graft function, and African American race as the most predictive risk factors of 30-day readmission. Additionally, significant variations in the therapeutic management of blood glucose by providers were observed. CONCLUSIONS: Suboptimal glucose metrics during hospitalization after kidney transplantation are associated with an increased risk for 30-day hospital readmission. Optimizing hospital blood glucose management, a modifiable factor, after kidney transplantation may reduce the risk of 30-day readmission.

Subclinical Pancreas Rejection on Protocol Biopsy Within the First Year of Simultaneous Pancreas Kidney Transplant.

This single-center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post-transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24-24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.

Favorable outcomes in Hispanic recipients receiving simultaneous pancreas kidney transplantation.

The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.

VO2peak prior to transplant differentiates survival post kidney transplant.

The OPTN/UNOS utilizes the calculated estimated posttransplant survival (EPTS) score as the measure of post-kidney transplant survival to guide allocation of deceased donor kidney transplantation. This score does not include any metric of functional capacity. Peak oxygen uptake (VO2peak ), is an established predictor of survival among both the general and diseased populations. We assessed the association and discriminative capacity of VO2peak and that of EPTS score and all-cause mortality post-kidney transplant. Additionally, we assessed the "mortality risk" lower VO2peak conferred on those patients with low EPTS score. Among a cohort of 293 transplant recipients with at least 3-years post-transplant follow-up, the median VO2peak was 15.0 ml/Kg/min. Lower pre-transplant VO2peak and higher EPTS score conferred higher risk of post-transplant mortality. Among the cohort of "low-risk" patients (patients with EPTS score < 50) those with lower VO2peak had significantly higher risk of mortality (log rank p = 0.045). In fact, the mortality risk among those with low-EPTS (< 50) and low VO2peak  < 12 ml/Kg/min was equivalent to those with high EPTS (> 80) score. We concluded functional capacity as defined by VO2peak is an important reflection of post-transplant survival. VO2peak is able to identify those with low EPTS who have similar survival to that of high EPTS phenotype.

Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient.

BACKGROUND: Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear. METHODS: Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient. RESULTS: The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure. CONCLUSIONS: Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.

Comparison of high glomerular filtration rate thresholds for identifying hyperfiltration.

BACKGROUND: High glomerular filtration rate (GFR) is often used as a surrogate for single-nephron hyperfiltration. Our objective was to determine the definition for high GFR that best reflects clinical and structural characteristics of hyperfiltration. METHODS: We studied living kidney donors at the Mayo Clinic and Cleveland Clinic. Potential donors underwent evaluations that included measured GFR (mGFR) by iothalamate clearance and estimated GFR (eGFR) by the serum creatinine-based Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI) equation. High GFR was defined by the 95th percentile for each method (mGFR or eGFR) using either overall or age-specific thresholds. High mGFR was defined as both corrected and uncorrected for body surface area. The association of high GFR by each definition with clinical characteristics and radiologic findings (kidney volume) was assessed. In the subset that donated, the association of high GFR with kidney biopsy findings (nephron number and glomerular volume) and single-nephron GFR was assessed. RESULTS: We studied 3317 potential donors, including 2125 actual donors. The overall 95th percentile for corrected mGFR was 134 mL/min/1.73 m2 and for eGFR was 118 mL/min/1.73 m2. The age-based threshold for uncorrected mGFR was 198 mL/min - 0.943×Age, for corrected mGFR it was 164 mL/min/1.73 m2 - 0.730×Age and for eGFR it was 146 mL/min/1.73 m2 - 0.813×Age. High age-based uncorrected mGFR had the strongest associations with higher single-nephron GFR, larger glomerular volume, larger kidney volume, male gender, higher body mass index and higher 24-h urine albumin, but also had the strongest association with high nephron number. A high age-height-gender-based uncorrected mGFR definition performed almost as well but had a weaker association with nephron number and did not associate with male gender. CONCLUSIONS: High age-based uncorrected mGFR showed the most consistent associations reflective of hyperfiltration. However, high age-based uncorrected mGFR has limited clinical utility because it does not distinguish between hyperfiltration and high nephron number.

Larger nephron size, low nephron number, and nephrosclerosis on biopsy as predictors of kidney function after donating a kidney.

It is unclear whether structural findings in the kidneys of living kidney donors predict postdonation kidney function. We studied living kidney donors who had a kidney biopsy during donation. Nephron size was measured by glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area. Age-specific thresholds were defined for low nephron number (calculated from CT and biopsy measures) and nephrosclerosis (global glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis). These structural measures were assessed as predictors of postdonation measured GFR, 24-hour urine albumin, and hypertension. Analyses were adjusted for baseline age, gender, body mass index, systolic and diastolic blood pressure, hypertension, measured GFR, urine albumin, living related donor status, and time since donation. Of 2673 donors, 1334 returned for a follow-up visit at a median 4.4 months after donation, with measured GFR <60 mL/min/1.73 m2 in 34%, urine albumin >5 mg/24 h in 13%, and hypertension in 5.3%. Larger glomerular volume and interstitial fibrosis/tubular atrophy predicted follow-up measured GFR <60 mL/min/1.73 m2 . Larger cortex volume per glomerulus and low nephron number predicted follow-up urine albumin >5 mg/24 h. Arteriosclerosis predicted hypertension. Microstructural findings predict GFR <60 mL/min/1.73 m2 , modest increases in urine albumin, and hypertension shortly after kidney donation.

Cardiac Troponin T and Right Ventricular Systolic Pressure Predict Cardiovascular and Mortality Risk in Kidney Transplant Candidates.

BACKGROUND: Patients presenting for kidney transplant (KTx) evaluation are subject to high rates of mortality and cardiovascular (CV) events pre- and post-KTx. CV and mortality risk assessment is needed. METHODS: We evaluated cardiac troponin T (cTnT) as a predictor of CV events and mortality in a racially diverse cohort with significant CV disease burden presenting for KTx evaluation. Right ventricular systolic pressure (RVSP) was also assessed in predicting these outcomes. The population consisted of 561 patients presenting for KTx evaluation from 2011 to 2013 at Mayo Clinic, Arizona. A cutoff value for cTnT and RVSP that was most associated with CV events or mortality was derived. Multivariate Cox regression analysis was used to assess cTnT, RVSP, traditional, and other risk factors for the outcomes of interest. RESULTS: Mean age was 53.5 ± 13.7 years and the median follow-up after KTx evaluation was 48.0 months. The cohort was 70.6% (n = 392) White, 11.4% (n = 63) Black, 8.5% (n = 47) Native American, and 3.1% (n = 17) Asian. Preexisting CV disease at the time of evaluation was prevalent in 24.4% (n = 137) of patients. During follow-up, 66.3% (n = 372) received a KTx and 21.9% (n = 123) had a composite event (16.8% death, 6.6 % CV events). It was found that 70.7% (n = 87) of events occurred in patients who were not transplanted; 53.5% (n = 300) had an elevated cTnT (≥0.01 ng/mL, median 0.02 ng/mL) and 84.1% (n = 344) of patients with RVSP data had an elevated RVSP (>25 mm Hg). Time to event analysis identified a cTnT ≥0.036 ng/mL and RVSP ≥31 mm Hg to be best predictive of CV events and mortality. Smoking, CV disease, hypoalbuminemia, RVSP, and cTnT independently predicted CV events and mortality. CONCLUSION: Elevated cTnT and RVSP were independently predictive of CV events and mortality in the cohort. Clinicians should consider the value of RVSP and cTnT as markers of CV risk in KTx evaluation.

Increasing Medical Student Interest in Nephrology.

BACKGROUND: Interest in nephrology careers is declining, possibly due to perceptions of the field and/or training aspects. Understanding practices of medical schools successfully instilling nephrology interest could inform efforts to attract leading candidates to the specialty. METHODS: The American Society of Nephrology Workforce Committee's Best Practices Project was one of several initiatives to increase nephrology career interest. Board-certified nephrologists graduating medical school between 2002 and 2009 were identified in the American Medical Association Masterfile and their medical schools ranked by production. Renal educators from the top 10 producing institutions participated in directed focus groups inquiring about key factors in creating nephrology career interest, including aspects of their renal courses, clinical rotations, research activities, and faculty interactions. Thematic content analysis of the transcripts (with inductive reasoning implementing grounded theory) was performed to identify factors contributing to their programs' success. RESULTS: The 10 schools identified were geographically representative, with similar proportions of graduates choosing internal medicine (mean 26%) as the national graduating class (26% in the 2017 residency Match). Eighteen educators from 9 of these 10 institutions participated. Four major themes were identified contributing to these schools' success: (1) nephrology faculty interaction with medical students; (2) clinical exposure to nephrology and clinical relevance of renal pathophysiology materials; (3) use of novel educational modalities; and (4) exposure, in particular early exposure, to the breadth of nephrology practice. CONCLUSION: Early and consistent exposure to a range of clinical nephrology experiences and nephrology faculty contact with medical students are important to help generate interest in the specialty.

The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging.

Nephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume×glomerular density. Donors 18-29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70-75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons.

Peripheral arterial disease preoperatively may predict graft failure and mortality in kidney transplant recipients.

Patients with end-stage renal disease undergoing kidney transplant often have diffuse atherosclerosis and high cardiovascular morbidity and mortality rates. We analyzed the correlation of peripheral arterial disease (PAD), here quantified by an abnormal ankle-brachial index (ABI) measured within the 5 years prior to kidney transplant, with graft failure and mortality rates (primary end points) after adjusting for known cardiovascular risk factors (age, sex, smoking history, hypertension, diabetes, stroke, known coronary artery disease or heart failure, years of dialysis). Of 1055 patients in our transplant population, 819 had arterial studies within the 5 years prior to transplant. Secondary end points included myocardial infarction; cerebrovascular accident; and limb ischemia, gangrene, or amputation. Low ABI was an independent and significant predictor of organ failure (OR, 2.77 (95% CI, 1.68-4.58), p<0.001), secondary end points (HR, 1.39 (95% CI, 0.97-1.99), p<0.076), and death (HR, 1.84 (95% CI, 1.26-2.68), p=0.002). PAD was common in this population: of 819 kidney transplant recipients, 46% had PAD. Low ABI was associated with a threefold greater risk of graft failure, a twofold greater risk of death after transplant, and a threefold greater risk of secondary end points. Screening for PAD is important in this patient population because of the potential impact on long-term outcomes.

Detection and Clinical Patterns of Nephron Hypertrophy and Nephrosclerosis Among Apparently Healthy Adults.

BACKGROUND: Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear. STUDY DESIGN: Cross-sectional (clinical-pathologic correlation). SETTING & PARTICIPANTS: Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011. PREDICTORS: Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness. OUTCOMES: Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation. RESULTS: Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis. LIMITATIONS: Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings. CONCLUSIONS: Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors.

Glucose homeostasis after simultaneous pancreas and kidney transplantation: a comparison of subjects with C-peptide-positive non-type 1 diabetes mellitus and type 1 diabetes mellitus.

BACKGROUND: While simultaneous pancreas kidney transplant (SPKTx) is a therapeutic option for patients with type 1 diabetes (T1DM) and renal failure, few centers offer SPKTx to "select" non-T1DM patients. To address concerns that existing insulin resistance may limit the benefits of the pancreas allograft among non-T1DM, we compared several indices of glucose homeostasis, in "select" non-T1DM and T1DM patients who received SPKTx. METHODS: Criteria for "select" non-T1DM included the following: positive C-peptide, BMI <30 kg/m(2) , treatment with oral agents before insulin initiation, and insulin at <1 unit/kg/d. We compared several indices of glucose homeostasis within 1 yr post-SPKTx among seven "select" patients with non-T1DM and nine patients with T1DM with similar age, BMI, and immunosuppression. Measurements of insulin resistance included the following: homeostatic model, insulin sensitivity index, and insulin-glucose ratio; insulin secretion measures included the following: corrected insulin response. RESULTS: Non-T1DM had similar pre-transplant metabolic (fasting glucose, HbA1c, blood pressure, and lipid) parameters to the T1DM cohort. There were no significant differences in the various measures of insulin resistance and secretion between T1DM and "select" non-T1DM patients. CONCLUSION: Our results suggest SPKTx should be considered in the therapeutic armamentarium among carefully select non-T1DM with features of minimal insulin resistance; however, a larger cohort with longer follow-up is needed to confirm our results.

Carfilzomib: A cause of drug associated thrombotic microangiopathy.

Carfilzomib is a selective proteosome inhibitor approved for treatment of relapsed and refractory multiple myeloma. Recent reports have linked exposure to carfilzomib with development of thrombotic microangiopathy (TMA). We describe two cases of biopsy proven thrombotic microangiopathy that occurred after the initiation of carfilzomib (dosed at 32 mg/m(2) and 23 mg/m(2), respectively) for relapsed multiple myeloma. Both patients were managed with discontinuation of the drug, therapeutic plasma exchange (TPE) and supportive care. Hemoglobin, platelets and renal function did not improve with TPE. TMA resolved with creatinine returning to baseline several weeks after discontinuation of the drug. The outcomes suggest that TPE is not beneficial for treating carfilzomib-induced TMA.

Distinguishing age-related from disease-related glomerulosclerosis on kidney biopsy: the Aging Kidney Anatomy study.

BACKGROUND: Global glomerulosclerosis is characteristic of chronic kidney disease and also occurs with normal aging. Our goal was to determine the upper limit of normal for number of globally sclerotic glomeruli. METHODS: Core-needle biopsies of the renal cortex were obtained at the time of living kidney transplantation at three centers between 1998 and 2011. The number of globally sclerotic glomeruli was averaged across two biopsy sections. Quantile regression was used to estimate the 95th percentile for globally sclerotic glomeruli as the upper reference limit. There were 2052 donors (mean age 43 years, 41% male, 10% hypertensive), with a mean (SD) of 16.0 (9.7) glomeruli and 0.47 (0.99) globally sclerotic glomeruli on biopsy; only 2.6% had >5% fibrosis. RESULTS: In a multivariable model excluding hypertensive donors, independent predictors of the number of globally sclerotic glomeruli were age, total number of glomeruli and cortex area. A simplified model was used to estimate the 95th percentile for number of globally sclerotic glomeruli by total number of glomeruli and age. For a biopsy section with 17-32 total glomeruli, the 95th percentile ranged from 1 for a 20-year old to 5.5 for a 70-year old donor. Hypertensive donors were more likely to have an abnormal number of globally sclerotic glomeruli (OR = 1.79, P = 0.035). CONCLUSIONS: We have derived the 95% reference limit for number of globally sclerotic glomeruli in ostensibly healthy individuals accounting for age and the biopsy characteristics. Numbers of globally sclerotic glomeruli in a kidney biopsy that exceed these thresholds suggest chronic pathological injury in excess of that expected with normal aging.

Age, kidney function, and risk factors associate differently with cortical and medullary volumes of the kidney.

The kidney atrophies in patients with advanced chronic kidney disease (CKD) but factors influencing kidney size in normal adults are less clear. To help define this, we measured kidney volumes on contrast-enhanced computed tomographic images from 1344 potential kidney donors (aged 18-75 years). Cortical volume per body surface area progressively declined in both genders with increased age. Statistically, this was primarily dependent on the age-related decline in glomerular filtration rate (GFR). Independent predictors of increased cortical volume per body surface area were male gender, increased GFR, increased 24-h urine albumin, current smoker, and decreased high-density lipid cholesterol. Medullary volume per body surface area increased with age in men, while it increased with age in women until the age of 50 years followed by a subsequent decline. Independent predictors of increased medullary volume per body surface area were older age, male gender, increased GFR, increased 24-h urine albumin, increased serum glucose, and decreased serum uric acid. Thus, while cortical volume declines with age along the same biological pathway as the age-related decline in GFR, albuminuria and some risk factors are actually associated with increased cortical or medullary volume among relatively healthy adults. Underlying hypertrophy or atrophy of different nephron regions may explain these findings.

Delayed allograft inflammation following alemtuzumab induction for kidney transplantation.

BACKGROUND: In a recent clinical trial in kidney transplant recipients, induction with alemtuzumab and rabbit-antithymocyte globulin (r-ATG) was equally effective in preventing rejection during the first post-transplant year; however, this study did not include protocol biopsies. METHODS: The aim of this study was to analyze the impact of alemtuzumab induction on rejection and subclinical inflammation during the first post-transplant year compared with a historic control group receiving induction with r-ATG. All patients received tacrolimus and mycophenolate mofetil (MMF). RESULTS: There were 361 in the alemtuzumab group and 478 in the r-ATG groups. Rejection (excluding Banff borderline), during the first year, occurred in 14% of the alemtuzumab group and 9% of the r-ATG group (p = 0.03). Estimated glomerular filtration rate (GFR) (chronic kidney disease (CKD)-EPI formula) at one yr and graft survival at three yr were similar. On the protocol biopsies, interstitial inflammation (Banff i scores) and tubulitis (Banff t scores) were more likely in the r-ATG group at one month, but at four and 12 months, both inflammation and tubulitis were more likely in the alemtuzumab group. CONCLUSIONS: We conclude that alemtuzumab induction is associated with delayed inflammation at four and 12 months, but this inflammation did not appear to negatively impact the GFR or graft survival.

Current State of Evidence on Kidney Transplantation: How Fragile Are the Results?

BACKGROUND: The study aims is to use the fragility index (FI) to examine the strength of evidence of randomized controlled trials (RCTs) published in the last decade on kidney transplantation. METHODS: We searched MEDLINE for studies on kidney transplantation. We included the RCTs that compared 2 groups with 1:1 randomization and reported significant P values (<0.05) for a dichotomous outcome and were published in the top 10 transplant journals. We calculated the FI; a calculation used to determine the minimum number of subjects needed to change from a nonevent to an event to make the study results nonsignificant (P ≥ 0.05). RESULTS: Fifty-seven RCTs met our inclusion criteria. The median sample size was 100 participants in each arm, the median number of events was 16 (interquartile range, 8-30) in the intervention group. Among the included trials, 79% were industry-funded, 93% involved medications, and the majority were open label. The median FI was 3 (interquartile range, 1-11). In 43% of the trials, the number of patients reported lost to follow-up was higher than or equal to the FI. Only 4% of the RCTs imputed a value for the missing dichotomous outcome. Furthermore, the median number of subjects who discontinued the trial because of adverse effects was 21, which was greater than the FI in 60% of the RCTs. CONCLUSIONS: The arbitrary classification of results into "significant" and "nonsignificant" based on P value <0.05 should perhaps be interpreted with the help of other statistical parameters and FI is one of them.