Publications by authors named "Sanjeev Akkina"

21 Publications

  • Page 1 of 1

Efficacy and Safety of Once-Daily LCP-Tacrolimus Versus Twice-Daily Immediate-Release Tacrolimus in Adult Hispanic Stable Kidney Transplant Recipients: Sub-Group Analysis from a Phase 3 Trial.

Ann Transplant 2021 Apr 16;26:e929535. Epub 2021 Apr 16.

Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.

BACKGROUND The pharmacokinetics and metabolism of tacrolimus, an immunosuppressant commonly used to prevent transplant rejection, can differ in specific subpopulations. This analysis examined treatment outcomes and safety of immediate-release tacrolimus (IR-Tac) and LCP-tacrolimus (LCPT) in stable Hispanic kidney transplant recipients. MATERIAL AND METHODS This was a post hoc analysis of clinical trial data from Hispanic adult stable kidney transplant recipients randomized to remain on IR-Tac or convert from IR-Tac to a reduced dose of LCPT (NCT00817206). Composite treatment failure was evaluated at 12 months. Estimated glomerular filtration rate and tacrolimus trough concentrations were evaluated over 12 months. RESULTS Fifty-five stable (LCPT n=26, IR-Tac n=29) kidney transplant recipients who self-identified as Hispanic or Latino were included in this analysis. Composite treatment failure occurred in 1 patient (4%) who converted to LCPT and 1 (3%) who remained on IR-Tac. The estimated glomerular filtration rate was stable over time and similar in the 2 treatment groups (P=0.08). Tacrolimus trough levels for both groups were similar over time in the 2 treatment groups (P=0.98). Treatment-emergent adverse events were similar in patients who converted to LCPT and in those who remained on IR-Tac. CONCLUSIONS Efficacy and safety were similar in Hispanic kidney transplant recipients who converted from IR-Tac to LCPT and in those remaining on IR-Tac.
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http://dx.doi.org/10.12659/AOT.929535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056872PMC
April 2021

Risks to Relationships in Kidney Transplant Research with Living Donors and Recipients.

Am J Bioeth 2021 04;21(4):110-112

Loyola University of Chicago, Stritch School of Medicine.

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http://dx.doi.org/10.1080/15265161.2021.1891330DOI Listing
April 2021

Health-Related Quality of Life, Depressive Symptoms, and Kidney Transplant Access in Advanced CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Kidney Med 2020 Sep-Oct;2(5):600-609.e1. Epub 2020 Aug 11.

Department of Medicine, Loyola University Medical Center, Maywood, IL.

Rationale & Objective: Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list.

Study Design: Prospective cohort study.

Setting & Population: 1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates ≤ 30 mL/min/1.73 m at study entry or during follow-up.

Exposures: HRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory.

Outcomes: Time to kidney transplant wait-listing and time to pre-emptive wait-listing.

Analytic Approach: Time-to-event analysis using Cox proportional hazards regression.

Results: During a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85;  < 0.001) and Effects scales (wait-listing aHR, 0.74; 95% CI, 0.59-0.92;  = 0.007). Participants with fewer depressive symptoms (ie, Beck Depression Inventory score < 14) had lower wait-listing rates than those with more depressive symptoms (aHR, 0.81; 95% CI, 0.66-0.99;  = 0.04). Participants with lower Burden and Effects scale scores and those with higher Symptoms and PCS scores had higher pre-emptive wait-listing rates (aHR in highest tertile of PCS relative to lowest tertile, 1.58; 95% CI, 1.12-2.23;  = 0.01).

Limitations: Unmeasured confounders.

Conclusions: Self-reported health in late-stage CKD may influence the timing of kidney transplantation.
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http://dx.doi.org/10.1016/j.xkme.2020.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568061PMC
August 2020

Kidney Transplantation for Erdheim-Chester Disease.

Case Rep Transplant 2020 13;2020:3954165. Epub 2020 Jul 13.

Department of Medicine, Transplant Nephrology, Loyola University Medical Center, Maywood, IL, USA.

Erdheim-Chester disease is a rare inflammatory disease that infiltrates skeletal and extra-skeletal tissue. Chronic kidney disease (CKD) in Erdheim-Chester disease is usually attributed to retroperitoneal lesions that lead to urologic obstruction and hydronephrosis. In this report, we describe a patient diagnosed with Erdheim-Chester disease who eventually developed end-stage kidney disease (ESKD). After complete remission of Erdheim-Chester disease by vemurafenib therapy and 2 years of hemodialysis, the patient underwent a deceased donor kidney transplantation with basiliximab induction and tacrolimus/mycophenolic acid maintenance. After conversion of mycophenolic acid to azathioprine due to cost, acute cellular rejection had occurred, and he was treated with steroid therapy. The patient remained in complete remission from Erdheim-Chester disease and dialysis-free 16 months after transplant. Kidney transplantation is another treatment option for those patients with Erdheim-Chester disease who suffer from renal failure in the setting of complete remission.
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http://dx.doi.org/10.1155/2020/3954165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374202PMC
July 2020

Cognitive Impairment in Non-Dialysis-Dependent CKD and the Transition to Dialysis: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Am J Kidney Dis 2018 10 2;72(4):499-508. Epub 2018 May 2.

Geriatric Research and Education Clinical Center, VA Palo Alto, Palo Alto, CA; Stanford University School of Medicine, Palo Alto, CA.

Background: Advanced chronic kidney disease is associated with elevated risk for cognitive impairment. However, it is not known whether and how cognitive impairment is associated with planning and preparation for end-stage renal disease.

Study Design: Retrospective observational study.

Setting & Participants: 630 adults participating in the CRIC (Chronic Renal Insufficiency Cohort) Study who had cognitive assessments in late-stage CKD, defined as estimated glome-rular filtration rate ≤ 20mL/min/1.73m, and subsequently initiated maintenance dialysis therapy.

Predictor: Predialysis cognitive impairment, defined as a score on the Modified Mini-Mental State Examination lower than previously derived age-based threshold scores. Covariates included age, race/ethnicity, educational attainment, comorbid conditions, and health literacy.

Outcomes: Peritoneal dialysis (PD) as first dialysis modality, preemptive permanent access placement, venous catheter avoidance at dialysis therapy initiation, and preemptive wait-listing for a kidney transplant.

Measurements: Multivariable-adjusted logistic regression.

Results: Predialysis cognitive impairment was present in 117 (19%) participants. PD was the first dialysis modality among 16% of participants (n=100), 75% had preemptive access placed (n=473), 45% avoided using a venous catheter at dialysis therapy initiation (n=279), and 20% were preemptively wait-listed (n=126). Predialysis cognitive impairment was independently associated with 78% lower odds of PD as the first dialysis modality (adjusted OR [aOR], 0.22; 95% CI, 0.06-0.74; P=0.02) and 42% lower odds of venous catheter avoidance at dialysis therapy initiation (aOR, 0.58; 95% CI, 0.34-0.98; P=0.04). Predialysis cognitive impairment was not independently associated with preemptive permanent access placement or wait-listing.

Limitations: Potential unmeasured confounders; single measure of cognitive function.

Conclusions: Predialysis cognitive impairment is associated with a lower likelihood of PD as a first dialysis modality and of venous catheter avoidance at dialysis therapy initiation. Future studies may consider addressing cognitive function when testing strategies to improve patient transitions to dialysis therapy.
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http://dx.doi.org/10.1053/j.ajkd.2018.02.361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153064PMC
October 2018

Predicting Fibrosis Progression in Renal Transplant Recipients Using Laser-Based Infrared Spectroscopic Imaging.

Sci Rep 2018 01 12;8(1):686. Epub 2018 Jan 12.

Department of Bioengineering, University of Illinois at Chicago, Chicago, USA.

Renal transplants have not seen a significant improvement in their 10-year graft life. Chronic damage accumulation often leads to interstitial fibrosis and tubular atrophy (IF/TA) and thus graft function loss over time. For this reason, IF/TA has been the chief suspect for a potential prognostic marker for long term outcomes. In this study, we have used infrared spectroscopic (IR) imaging to interrogate the biochemistry of regions of fibrosis from renal transplant biopsies to identify a biochemical signature that can predict rapid progression of fibrosis. IR imaging represents an approach that permits label-free biochemical imaging of human tissues towards identifying novel biomarkers for disease diagnosis or prognosis. Two cohorts were identified as progressors (n = 5, > 50% fibrosis increase between time points) and non-progressors (n = 5, < 5% increase between time points). Each patient had an early time point and late time point biopsy. Collagen associated carbohydrate moieties (ν(C-O), 1035 cm and ν(C-O-C),1079 cm) spectral ratios demonstrated good separation between the two cohorts (p = 0.001). This was true for late and early time point biopsies suggesting the regions of fibrosis are biochemically altered in cases undergoing progressive fibrosis. Thus, IR imaging can potentially predict rapid progression of fibrosis using histologically normal early time point biopsies.
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http://dx.doi.org/10.1038/s41598-017-19006-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766495PMC
January 2018

The Authors Reply.

Kidney Int 2016 07;90(1):226

Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, USA; Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, USA. Electronic address:

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http://dx.doi.org/10.1016/j.kint.2016.03.015DOI Listing
July 2016

Impact of Maintenance Steroids versus Rapid Steroid Withdrawal in African-American Kidney Transplant Recipients: Comparison of Two Urban Centers.

Int J Clin Med 2016;7:204-216

Department of Medicine, Division of Nephrology, Loyola University Medical Center, Maywood, IL, USA.

Background: Rapid steroid withdrawal (RSW) is used increasingly in kidney transplantation but long-term outcomes in African-American (AA) recipients are not well known. We compared 1 and 5 year transplant outcomes in a large cohort of AA patients who were maintained on continued steroid therapy (CST) to those who underwent RSW.

Methods: Post-transplant courses of A as receiving kidney allografts from 2003-2011 at two urban transplant centers in Chicago were followed. Prior to outcome analysis, we used Inverse Probability of Treatment Weights (IPTW) to match the two groups on a set of baseline risk factors. Graft and patient survival, GFR at 1 and 5 years, incidence and type of rejection, incidence of post-transplant diabetes mellitus (PTDM), delayed graft function, CMV and BK viremia were compared.

Results: There were 150 AA recipients in the CST analytic group and 157 in the RSW analytic group. Graft and patient survival was similar between the two groups. Rates of CMV viremia were higher in the RSW compared to the CST analytic group at 1 year. Biopsy-proven acute rejection and PTDM were similar between the RSW and CST groups.

Conclusions: In AA recipients, RSW has similar long-term outcomes to CST.
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http://dx.doi.org/10.4236/ijcm.2016.73021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829964PMC
January 2016

Serum β-Trace Protein and β2-Microglobulin as Predictors of ESRD, Mortality, and Cardiovascular Disease in Adults With CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Am J Kidney Dis 2016 Jul 3;68(1):68-76. Epub 2016 Mar 3.

Tufts Medical Center, Boston, MA. Electronic address:

Background: Serum β-trace protein (BTP) and β2-microglobulin (B2M) are independently associated with end-stage renal disease (ESRD) and mortality in the general population and high-risk groups with diabetes or advanced chronic kidney disease (CKD). Less is known about their associations with outcomes and predictive ability in adults with moderate CKD.

Study Design: Prospective cohort study.

Setting & Participants: 3,613 adults from the CRIC (Chronic Renal Insufficiency Cohort) Study (45% women; mean age, 57.9 years; 41.0% non-Hispanic black; 51.9% with diabetes).

Predictors: BTP and B2M levels with a reciprocal transformation to reflect their associations with filtration, creatinine-based estimated glomerular filtration rate (eGFRcr), measured GFR, and a 4-marker composite score combining BTP, B2M, creatinine, and cystatin C levels. Predictors were standardized as z scores for comparisons across filtration markers.

Outcomes: ESRD, all-cause mortality, and new-onset cardiovascular disease.

Results: During a 6-year median follow-up, 755 (21%) participants developed ESRD, 653 died, and 292 developed new-onset cardiovascular disease. BTP, B2M, and the 4-marker composite score were independent predictors of ESRD and all-cause mortality, and B2M and the 4-marker composite score of cardiovascular events, after multivariable adjustment. These associations were stronger than those observed for eGFRcr (P vs eGFRcr≤0.02). The 4-marker composite score led to improvements in C statistic and 2.5-year risk reclassification beyond eGFRcr for all outcomes.

Limitations: Filtration markers measured at one time point; measured GFR available in subset of cohort.

Conclusions: BTP and B2M levels may contribute additional risk information beyond eGFRcr, and the use of multiple markers may improve risk prediction beyond this well-established marker of kidney function among persons with moderate CKD.
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http://dx.doi.org/10.1053/j.ajkd.2016.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921300PMC
July 2016

A label-free approach by infrared spectroscopic imaging for interrogating the biochemistry of diabetic nephropathy progression.

Kidney Int 2016 May 2;89(5):1153-1159. Epub 2016 Feb 2.

Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, USA; Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, USA. Electronic address:

Routine histology, the current gold standard, involves staining for specific biomolecules. However, untapped biochemical information in tissue can be gathered using biochemical imaging. Infrared spectroscopy is an emerging modality that allows label-free chemical imaging to derive biochemical information (such as protein, lipids, DNA, collagen) from tissues. Here we employed this technology in order to better predict the development of diabetic nephropathy. Using human primary kidney biopsies or nephrectomies, we obtained tissue from 4 histologically normal kidneys, 4 histologically normal kidneys from diabetic subjects, and 5 kidneys with evidence of diabetic nephropathy. A biochemical signature of diabetic nephropathy was derived that enabled prediction of nephropathy based on the ratio of only 2 spectral frequencies. Nonetheless, using the entire spectrum of biochemical information, we were able to detect renal disease with near-perfect accuracy. Additionally, study of sequential protocol biopsies from 3 transplanted kidneys showed biochemical changes even prior to clinical manifestation of diabetic nephropathy. Thus, infrared imaging can identify critical biochemical alterations that precede morphologic changes, potentially allowing for earlier intervention.
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http://dx.doi.org/10.1016/j.kint.2015.11.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834260PMC
May 2016

High-definition Fourier Transform Infrared (FT-IR) spectroscopic imaging of human tissue sections towards improving pathology.

J Vis Exp 2015 Jan 21(95):52332. Epub 2015 Jan 21.

Department of Pathology, University of Illinois at Chicago;

High-definition Fourier Transform Infrared (FT-IR) spectroscopic imaging is an emerging approach to obtain detailed images that have associated biochemical information. FT-IR imaging of tissue is based on the principle that different regions of the mid-infrared are absorbed by different chemical bonds (e.g., C=O, C-H, N-H) within cells or tissue that can then be related to the presence and composition of biomolecules (e.g., lipids, DNA, glycogen, protein, collagen). In an FT-IR image, every pixel within the image comprises an entire Infrared (IR) spectrum that can give information on the biochemical status of the cells that can then be exploited for cell-type or disease-type classification. In this paper, we show: how to obtain IR images from human tissues using an FT-IR system, how to modify existing instrumentation to allow for high-definition imaging capabilities, and how to visualize FT-IR images. We then present some applications of FT-IR for pathology using the liver and kidney as examples. FT-IR imaging holds exciting applications in providing a novel route to obtain biochemical information from cells and tissue in an entirely label-free non-perturbing route towards giving new insight into biomolecular changes as part of disease processes. Additionally, this biochemical information can potentially allow for objective and automated analysis of certain aspects of disease diagnosis.
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http://dx.doi.org/10.3791/52332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395079PMC
January 2015

Relation of serum lipids and lipoproteins with progression of CKD: The CRIC study.

Clin J Am Soc Nephrol 2014 Jul 15;9(7):1190-8. Epub 2014 May 15.

Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, Pennsylvania;

Background And Objectives: Hyperlipidemia is common in patients with CKD. The objective of this study was to evaluate whether measures of plasma lipids and lipoproteins predict progression of kidney disease in patients with CKD.

Design, Setting, Participants, & Measurements: Prospective cohort study in adults (n=3939) with CKD aged 21-74 years recruited between 2003 and 2008 and followed for a median of 4.1 years. At baseline, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), apoA-I , apoB, and lipoprotein(a) [Lp(a)] were measured. The outcomes were composite end point of ESRD or 50% decline in eGFR from baseline (rate of change of GFR).

Results: Mean age of the study population was 58.2 years, and the mean GFR was 44.9 ml/min per 1.73 m(2); 48% of patients had diabetes. None of the lipid or lipoprotein measures was independently associated with risk of the composite end point or rate of change in GFR. However, there were significant (P=0.01) interactions by level of proteinuria. In participants with proteinuria<0.2 g/d, 1-SD higher LDL-C was associated with a 26% lower risk of the renal end point (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59 to 0.92; P=0.01), and 1-SD higher total cholesterol was associated with a 23% lower risk of the renal end point (HR, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In participants with proteinuria>0.2 g/d, neither LDL-C (HR, 0.98; 95% CI, 0.98 to 1.05) nor total cholesterol levels were associated with renal outcomes. Treatment with statins was reported in 55% of patients and was differential across lipid categories.

Conclusions: In this large cohort of patients with CKD, total cholesterol, triglycerides, VLDL-C, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) were not independently associated with progression of kidney disease. There was an inverse relationship between LDL-C and total cholesterol levels and kidney disease outcomes in patients with low levels of proteinuria.
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http://dx.doi.org/10.2215/CJN.09320913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078958PMC
July 2014

Prevalence of 25-OH vitamin D deficiency in a population of hemodialysis patients and efficacy of an oral ergocalciferol supplementation regimen.

Am J Nephrol 2013 30;37(6):568-74. Epub 2013 May 30.

Department of Medicine, University of Illinois Hospital and Health Sciences System, Chicago, Ill., USA.

Background/aims: Optimal dosing regimens for 25-OH vitamin D (VitD) deficiency are unknown in hemodialysis (HD) patients. Our aim was to evaluate the efficacy of prescribing ergocalciferol supplementation based on KDOQI guidelines for chronic kidney disease (CKD) stages III-IV in HD patients.

Methods: We conducted a retrospective study of 96 urban, predominately African-American HD patients at a single-center dialysis unit with VitD insufficiency or deficiency treated with ergocalciferol. Patients were classified as either compliant or non-compliant with supplementation as determined by review of pharmacy records. The primary outcome was VitD levels 6 months after initiation of treatment and secondary outcomes were VitD levels at 11 months, bone/mineral and anemia parameters.

Results: The population was predominately African-American (69%) and Hispanic (28%). There were 61 individuals in the compliant group and 35 individuals in the non-compliant group. The compliant group was older but otherwise similar in demographics and co-morbid conditions to the non-compliant group. After 6 months of treatment, the compliant group had a significant increase in VitD level (14.7 ± 6.0 to 28.7 ± 10.0 ng/ml, p < 0.0001) compared to the non-compliant group (14.7 ± 5.5 to 14.8 ± 7.1 ng/ml, p = 0.95). There were no differences in the incidence of hypercalcemia between the two groups. Except for a decrease in phosphorus in the compliant group (5.6 ± 1.6 to 4.9 ± 1.7 mg/dl, p = 0.004), there were no significant difference in bone/mineral or anemia parameters including dosing of darbepoetin.

Conclusion: An ergocalciferol-prescribing strategy using the KDOQI guidelines for stage III-IV kidney disease in HD patients with VitD deficiency or insufficiency is inadequate to achieve repletion or maintenance of normal VitD levels.
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http://dx.doi.org/10.1159/000351185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109679PMC
October 2013

Illicit drug use, hypertension, and chronic kidney disease in the US adult population.

Transl Res 2012 Dec 23;160(6):391-8. Epub 2012 Jun 23.

Medicine/Nephrology, University of Illinois at Chicago, Chicago, IL 60612-7315, USA.

Illicit drug use has been associated with chronic kidney disease (CKD) in select populations, but it is unknown whether the same association exists in the general population. By using data from the National Health and Nutrition Examination Survey 2005-2008, we conducted a cross-sectional analysis of 5861 adults who were questioned about illicit drug use, including cocaine, methamphetamines, and heroin, during their lifetime. The primary outcome was CKD as defined by an estimated glomerular filtration rate ≤60 mL/min/1.73 m(2) using the Chronic Kidney Disease Epidemiology Collaboration equation or by microalbuminuria. We also examined the association between illicit drug use and blood pressure (BP) ≥120/80, ≥130/85, and ≥140/90 mm Hg. Logistic regression was used to examine the association between illicit drug use and CKD and BP. Mean estimated glomerular filtration rate was similar between illicit drug users and nonusers (100.7 vs 101.4 mL/min/1.73 m(2), P = 0.4), as was albuminuria (5.7 vs 6.0 mg/g creatinine, P = 0.5). Accordingly, illicit drug use was not significantly associated with CKD in logistic regression models (odds ratio [OR], 0.98; confidence interval [CI], 0.75-1.27) after adjusting for other important factors. However, illicit drug users had higher systolic (120 vs 118 mm Hg, P = 0.04) and diastolic BP (73 vs 71 mm Hg, P = 0.0003) compared with nonusers. Cocaine use was independently associated with BP ≥130/85 mm Hg (OR, 1.24; CI, 1.00-1.54), especially when used more during a lifetime (6-49 times; OR, 1.42; CI, 1.06-1.91). In a representative sample of the US population, illicit drug use was not associated with CKD, but cocaine users were more likely to have elevated BP.
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http://dx.doi.org/10.1016/j.trsl.2012.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461092PMC
December 2012

Creatinine-based estimations of kidney function are unreliable in obese kidney donors.

J Transplant 2012 19;2012:872894. Epub 2012 Jan 19.

Department of Medicine, University of Illinois at Chicago, 820 S. Wood Street, M/C 793, Chicago, IL 60612-7315, USA.

Accurate assessment of kidney function by measurement of glomerular filtration rate (GFR) is essential to the risk assessment of prospective living kidney donors. We evaluated the performance of various estimating equations for creatinine clearance (Cockcroft-Gault), GFR (Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration), and 24-hour urine collections for creatinine clearance in obese potential kidney donors. We evaluated 164 potential kidney donors including 49 with a BMI of 30-35 and 32 with a BMI >35 that have completed a routine living donor evaluation with a measured GFR. All the estimating equations performed poorly in obese donors. While 24-hour urine collections performed better, only 15% had an adequate 24-hour urine collection. Since obese kidney donors may be at higher than average risk for kidney failure, accurate assessment of kidney function in these donors is crucial to ensure their long-term health postdonation.
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http://dx.doi.org/10.1155/2012/872894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270458PMC
August 2012

Development of organ-specific donor risk indices.

Liver Transpl 2012 Apr;18(4):395-404

Department of Medicine, University of Illinois, Chicago, IL, USA.

Because of the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival with various combinations of donor and recipient characteristics. Here we review the kidney donor risk index (KDRI) and the liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The KDRI has a potential role in developing new kidney allocation algorithms. The LDRI allows a greater appreciation of the importance of donor factors, particularly for hepatitis C virus-positive recipients; as the donor risk index increases, the rates of allograft and patient survival among these recipients decrease disproportionately. The use of livers with high donor risk indices is associated with increased hospital costs that are independent of recipient risk factors, and the transplantation of livers with high donor risk indices into patients with Model for End-Stage Liver Disease scores < 15 is associated with lower allograft survival; the use of the LDRI has limited this practice. Significant regional variations in donor quality, as measured by the LDRI, remain in the United States. We also review other potential indices for liver transplantation, including donor-recipient matching and the retransplant donor risk index. Although substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival.
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http://dx.doi.org/10.1002/lt.23398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3332103PMC
April 2012

MicroRNAs in kidney function and disease.

Transl Res 2011 Apr 3;157(4):236-40. Epub 2011 Feb 3.

College of Medicine, University of Illinois at Chicago, Chicago, Ill, USA.

MicroRNAs (miRNA) are short, noncoding RNA sequences that regulate gene expression by blocking protein translation or inducing messenger RNA (mRNA) degradation. miRNA is found in various tissues with variable expression, and changes in expression are related to various disease processes. Evidence suggests that changes in miRNA expression are critical for the normal development of kidney tissue. Alternatively, in diseases such as diabetic nephropathy, polycystic kidney disease, and lupus nephritis, specific miRNAs may enhance disease manifestations in a myriad of ways, ranging from activation of fibrotic pathways to anatomic changes that abet proteinuria. The variable expression of miRNA in kidney tissue, whether in the context of normal development or disease processes, makes miRNAs a valuable new tool for understanding, diagnosing, and discovering therapeutic options for pathologic processes that affect the kidney.
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http://dx.doi.org/10.1016/j.trsl.2011.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062898PMC
April 2011

Donor exchange programs in kidney transplantation: rationale and operational details from the north central donor exchange cooperative.

Am J Kidney Dis 2011 Jan 8;57(1):152-8. Epub 2010 Aug 8.

Department of Medicine, University of Illinois at Chicago, USA.

The increasing need for kidney transplants has led to innovations such as donor exchange programs. These programs offer transplant recipients with incompatible donors an opportunity to receive a compatible kidney. They also provide an alternative to costly desensitization protocols that have unproven long-term outcomes. Donor exchange programs have multiple options, including simple 2-pair exchanges, more complicated domino exchanges, or chain donations. The United States currently is limited by regional programs that provide for kidney donor exchanges. However, with the increasing public interest in and need for kidney transplants, general nephrologists will be approached with questions about these donor exchange programs. The goal of this review is to discuss donor exchange programs, including their role in expanding the donor pool, various types of exchanges, regional centers that provide these programs, and the process involved in patient enrollment. General knowledge of donor exchange programs will help providers in discussing options with patients approaching end-stage kidney disease and transplant.
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http://dx.doi.org/10.1053/j.ajkd.2010.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980801PMC
January 2011

Appraisal of GFR-estimating equations following kidney donation.

Am J Kidney Dis 2009 Jun 25;53(6):1050-8. Epub 2009 Apr 25.

Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, MN 55414, USA.

Background: It is not clear which serum creatinine-based glomerular filtration rate (GFR)-estimating model performs best in kidney donors.

Study Design: Study of diagnostic accuracy.

Setting & Participants: From a population of 3,698 kidney donors, 255 donors underwent iohexol GFR measurement (mGFR). INDEX TEST (INTERVENTION): mGFR by means of plasma disappearance of iohexol.

Reference Test Or Outcome: GFR was estimated (eGFR) by using the Cockcroft-Gault equation (eGFR(CG)), Mayo Clinic equation (eGFR(MC)), and Modification of Diet in Renal Disease (MDRD) Study equation (eGFR(MDRD)).

Results: Mean mGFR was 71.8 +/- 11.8 mL/min/1.73 m(2), and 85.5% had mGFR greater than 60 mL/min/1.73 m(2). eGFR(CG) underestimated mGFR by 3.96 +/- 13.3 mL/min/1.73 m(2) and was within 30% of mGFR 89.4% of the time. eGFR(MC) overestimated mGFR by 8.44 +/- 11.9 mL/min/1.73 m(2) and was within 30% of mGFR in 83.1% of cases. eGFR(MDRD) underestimated mGFR by only 0.43 +/- 11.7 mL/min/1.73 m(2), and the proportion within 30% of mGFR was greatest in the tested model; 94.1% of the time. However, eGFR(MC) was most accurate in classifying donors according to having eGFR less than 60 mL/min/1.73 m(2).

Limitations: Lack of ethnic diversity and response bias.

Conclusions: The MDRD Study equation is least biased, and because it is routinely reported by most laboratories, it is the best readily available model for estimating GFR in kidney donors.
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http://dx.doi.org/10.1053/j.ajkd.2009.01.264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693296PMC
June 2009

Temporal stability of the urinary proteome after kidney transplant: more sensitive than protein composition?

J Proteome Res 2009 Jan;8(1):94-103

Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.

The temporal urinary proteome was examined in 4 groups of individuals in order to determine the temporal stability of diverse individuals with apparently good kidney health. The groups consisted of (1) healthy volunteers at zero time, 1 and 6 months, (2) kidney donors before and after surgery, (3) recipients immediately after surgery, and (4) successful kidney transplant recipients from 1 month to 4 years after transplant. Proteins were detected by reverse phase extraction of urine followed by MALDI-TOF profile and by iTRAQ analysis. Unusual components of the MALDI-TOF profiles found only in transplant subjects occurred at m/ z = 3370, 3441 and 3385 (human neutrophil defensins), 4303, 10350, and 11732 (beta-2 microglobulin, B2M). The peaks at m/ z = 4303 and 11732 were also quite intense among kidney donors following surgery. The peaks at m/ z = 4303 and 10350 in transplant recipients were associated with higher serum creatinine. Several additional proteins detected by iTRAQ were up-regulated in a manner that correlated closely with B2M. Overall, despite large differences between protein composition in different transplant recipients, there was remarkable stability for each individual as detected by either MALDI-TOF or iTRAQ analyses. These results suggested that, within limits, stability of profile components may be as important as protein content for definition of kidney health. Longitudinal study of urinary proteins from kidney recipients may demonstrate instability as a sensitive biomarker of adverse kidney health.
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http://dx.doi.org/10.1021/pr800646jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722382PMC
January 2009