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1.
Kidney Med ; 5(2): 100585, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36712315

ABSTRACT

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

3.
Clin Transplant ; 35(1): e14131, 2021 01.
Article in English | MEDLINE | ID: mdl-33112428

ABSTRACT

Eighty primary renal allograft recipients, 61 living-related and 19 deceased donor, transplanted from 1963 through 1984 had continuous graft function for 30-47 years. They were treated with three different early immunosuppression programs (1963-1970: thymectomy, splenectomy, high oral prednisone; 1971-1979: divided-dose intravenous methylprednisolone; and 1980-1984: antilymphocyte globulin) each with maintenance prednisone and azathioprine, and no calcineurin inhibitor. Long-term treatment often included the anti-platelet medication, dipyridamole. Although both recipient and donor ages were young (27.2 ± 9.5 and 33.1 ± 12.0 years, respectively), six recipients with a parent donor had >40-year success. At 35 years, death-censored graft survival was 85.3% and death with a functioning graft 84.2%; overall graft survival was 69.5% (Kaplan-Meier estimate). Biopsy-documented early acute cellular and highly probable antibody-mediated rejections were reversed with divided-dose intravenous methylprednisolone. Complications are detailed in an integrated timeline. Hypogammaglobulinemia identified after 20 years doubled the infection rate. An association between a monoclonal gammopathy of undetermined significance and non-plasma-cell malignancies was identified. Twenty-seven azathioprine-treated patients tested after 37 years had extremely low levels of T1/T2 B lymphocytes representing a "low immunosuppression state of allograft acceptance (LISAA)". The lifetime achievements of these patients following a single renal allograft and low-dose maintenance immunosuppression are remarkable. Their success evolved as a clinical mosaic.


Subject(s)
Kidney Transplantation , Mycophenolic Acid , Adolescent , Adult , Allografts , Antilymphocyte Serum , Azathioprine/therapeutic use , Drug Therapy, Combination , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/prevention & control , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Prednisone , Young Adult
4.
Cleve Clin J Med ; 2020 Dec 03.
Article in English | MEDLINE | ID: mdl-33272970

ABSTRACT

Although the literature is limited, early evidence suggests that patients with chronic kidney disease, end-stage kidney disease, and kidney transplant recipients are at increased risk for severe COVID-19 disease and death. Hence, management should focus on both infection prevention and treatment. There is currently a lack of evidence and guideline recommendations on optimal management of immunosuppression in kidney transplant recipients with COVID-19 infection. This article focuses on the prevention and management of COVID-19 in patients with chronic kidney disease, patients with end-stage kidney disease on home hemodialysis and peritoneal dialysis, and kidney transplant recipients.

5.
Clin Transplant ; 33(6): e13583, 2019 06.
Article in English | MEDLINE | ID: mdl-31038773

ABSTRACT

OBJECTIVE: Urinary tract infections (UTIs) are the most commonly occurring infectious complication following kidney transplantation. Questions remain regarding whether asymptomatic bacteriuria (ASB) should be treated. The aim was to evaluate the incidence and management of ASB in kidney transplant recipients at a large academic medical center. METHODS: All subjects receiving an isolated kidney transplant between September 2012 and October 2016, and with at least one ASB episode were included. Demographics, symptomatology, and urine culture data were collected on subjects with bacteriuria in the first year post-transplant. Cultures were classified by symptoms, ASB treatment trends were analyzed, and ASB-to-UTI progression was compared between ASB treatment and non-treatment. RESULTS: A total of 527 subjects were transplanted with 64 developing at least one ASB episode. The incidence of ASB was 12.1% and treated 74.6% of the time. Neither lack of ASB treatment (P = 0.463) nor ASB within the first month post-transplant (P = 0.303) were associated with ASB-to-UTI progression. CONCLUSION: Despite high ASB treatment rate, this was not found to be protective against ASB-to-UTI progression. ASB within the first month post-transplant also did not correlate with increased progression risk. These results suggest minimization of ASB treatment in kidney transplant recipients remains an important antimicrobial stewardship target.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteriuria/epidemiology , Kidney Transplantation/adverse effects , Postoperative Complications/drug therapy , Urinary Tract Infections/drug therapy , Aged , Bacteriuria/complications , Bacteriuria/drug therapy , Disease Management , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Ohio/epidemiology , Postoperative Complications/etiology , Postoperative Complications/pathology , Prognosis , Retrospective Studies , Risk Factors , Urinalysis , Urinary Tract Infections/etiology , Urinary Tract Infections/pathology
6.
Pharmacotherapy ; 37(12): 1507-1515, 2017 12.
Article in English | MEDLINE | ID: mdl-28976570

ABSTRACT

BACKGROUND: Pharmacokinetic data show reduced mycophenolic acid levels in renal transplant recipients taking mycophenolate mofetil (MMF) and proton pump inhibitors (PPIs) concomitantly. This reduced exposure could increase rejection risk. The typical initial MMF dose post renal transplantation is 2 g/day, which often requires dose reduction secondary to side effects. Existing studies have not shown significant acute rejection differences for patients taking MMF-PPI versus patients taking MMF-ranitidine. OBJECTIVE: The purpose of this study was to evaluate clinical outcomes in renal transplant recipients receiving a lower MMF dose than previously studied (1.5 g/day) and either a PPI or histamine-2 receptor antagonist (H2RA). METHODS: This retrospective cohort study included adult subjects receiving a renal transplant between January 1, 2009, and June 30, 2013. Comparison groups were defined based on acid-suppressing therapy class prescribed at discharge from transplantation. The primary outcome was acute rejection incidence within 1 year posttransplantation. RESULTS: Of 728 renal transplant recipients screened, 522 were included: 183 taking a PPI and 339 taking an H2RA. There was no significant difference in acute rejection within 1 year (H2RA 19% versus PPI 14%, p=0.12) or 3 months (4% vs 5%, p=0.44, respectively) posttransplantation. Maintenance immunosuppression (MMF dose and tacrolimus troughs) was similar between groups at 3 months and 1 year. Graft and patient survivals were favorable (> 95%), and graft function at 1 year was stable and similar between groups. CONCLUSION: Despite taking lower MMF doses than previously studied, subjects on a PPI compared to an H2RA were not at increased risk of acute rejection within 1 year posttransplantation.


Subject(s)
Drug Therapy, Combination/adverse effects , Graft Rejection/drug therapy , Histamine H2 Antagonists/adverse effects , Kidney Transplantation/methods , Mycophenolic Acid/adverse effects , Proton Pump Inhibitors/adverse effects , Adult , Drug Interactions , Female , Histamine H2 Antagonists/therapeutic use , Humans , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Proton Pump Inhibitors/therapeutic use , Retrospective Studies
7.
Clin J Am Soc Nephrol ; 9(5): 881-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24721888

ABSTRACT

BACKGROUND AND OBJECTIVES: The two largest studies of mammalian target of rapamycin inhibitor treatment of autosomal dominant polycystic kidney disease (ADPKD) demonstrated no clear benefit on the primary endpoint of total kidney volume (TKV) or on eGFR. The present study evaluated two levels of rapamycin on the 12-month change in (125)I-iothalamate GFR (iGFR) as the primary endpoint and TKV secondarily. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a 12-month open-label pilot study, 30 adult patients with ADPKD were randomly assigned to low-dose (LD) rapamycin (rapamycin trough blood level, 2-5 ng/ml) (LD group, n=10), standard-dose (STD) rapamycin trough level (>5-8 ng/ml) (STD group, n=10), or standard care (SC group, n=10). They were evaluated with iGFR and noncontrast computed tomography. RESULTS: Change in iGFR at 12 months was significantly higher in the LD group (7.7±12.5 ml/min per 1.73 m(2); n=9) than in the SC group (-11.2 ± 9.1 ml/min per 1.73 m(2); n=9) (LD versus SC: P<0.01). Change in iGFR at 12 months in the STD group (1.6 ± 12.1 ml/min per 1.73 m(2); n=8) was not significantly greater than that in the SC group (P=0.07), but it was in the combined treatment groups (LD+STD versus SC: P<0.01). Neither eGFR calculated by the CKD-Epidemiology Collaboration equation nor TKV (secondary endpoint) changed significantly from baseline to 12 months in any of the groups. On the basis of results of the mixed model, during the study, patients in the LD group had significantly lower trough blood levels of rapamycin (mean range ± SD, 2.40 ± 0.64 to 2.90 ± 1.20 ng/ml) compared with those in the STD group (3.93 ± 2.27 to 5.77 ± 1.06 ng/ml) (P<0.01). CONCLUSION: Patients with ADPKD receiving LD rapamycin demonstrated a significant increase in iGFR compared with those receiving standard care, without a significant effect on TKV after 12 months.


Subject(s)
Enzyme Inhibitors/administration & dosage , Kidney/pathology , Polycystic Kidney, Autosomal Dominant/drug therapy , Polycystic Kidney, Autosomal Dominant/physiopathology , Sirolimus/administration & dosage , Adult , Aged , Arterial Pressure , Enzyme Inhibitors/blood , Female , Glomerular Filtration Rate , Humans , Kidney/diagnostic imaging , Male , Middle Aged , Organ Size/drug effects , Pilot Projects , Polycystic Kidney, Autosomal Dominant/pathology , Sirolimus/blood , TOR Serine-Threonine Kinases/antagonists & inhibitors , Tomography, X-Ray Computed , Young Adult
8.
Clin Transplant ; 27(3): E230-6, 2013.
Article in English | MEDLINE | ID: mdl-23551281

ABSTRACT

BACKGROUND: Reduction in immunosuppression is considered the therapy of proven benefit for BKV infection in renal transplantation, but the use of leflunomide has also been reported. It was observed at this center that the patterns of viral load response while on leflunomide appear to fall into two distinct types. METHODS: Medical records of 22 kidney and kidney-pancreas recipients at a single center who received leflunomide therapy for BKV DNAemia were reviewed. Information was collected on demographics, BKV viral loads, other antiviral therapy, immunosuppressive drug levels and doses, adverse effects, and graft and patient outcomes. RESULTS: Eighteen of 22 cleared BKV viremia, and 12 of 22 had preserved allograft function; only two graft losses occurred in the screening era among leflunomide-treated patients. Two patterns of viral load reduction were observed, termed the "smooth" and the "zigzag" pattern, which differed in mean time to clear of BKV DNA (2.9 vs. 19.5 months, p = 0.0073). Graft preservation was correlated with lower serum creatinine (SCr) at the start of leflunomide therapy. CONCLUSIONS: Long courses and "zigzag" fluctuations in viral load can occur in patients who eventually clear BKV on leflunomide with preserved allograft function. Intermittent increases in viral load do not necessarily portend therapeutic failure. Although the utility of leflunomide is still debated in the transplant community, this information may be useful to clinicians who choose to use it in selected patients.


Subject(s)
BK Virus/drug effects , DNA, Viral/blood , Isoxazoles/therapeutic use , Kidney Transplantation , Polyomavirus Infections/immunology , Tumor Virus Infections/immunology , Viral Load/immunology , BK Virus/immunology , Female , Graft Rejection/immunology , Humans , Immunosuppressive Agents/therapeutic use , Leflunomide , Male , Polyomavirus Infections/drug therapy , Polyomavirus Infections/virology , Tumor Virus Infections/drug therapy , Tumor Virus Infections/virology , Viremia/immunology
9.
Clin J Am Soc Nephrol ; 8(1): 19-25, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23037982

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients with AKI after lung transplantation are at increased risk for CKD and death. Whether patients who completely recover from AKI have improved long-term outcome compared with patients who do not completely recover remains unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study retrospectively evaluated data on 657 patients who underwent lung transplantation from 1997 to 2009. Outcomes analyzed were the incidence of renal recovery after AKI and the association of this recovery with short- and long-term mortality. AKI was defined by an absolute increase in serum creatinine of ≥0.3 mg/dl or a percent increase in serum creatinine of ≥50% from baseline at any time during the first 2 weeks after transplantation. RESULTS: Four hundred twenty-four (65%) patients experienced AKI in the first 2 weeks after transplantation. Of these patients, complete renal recovery occurred in 142 (33%) patients. The incidence of in-hospital complications was similar between patients who recovered renal function and patients without recovery. At 1 year, the cumulative incidence of CKD was 14% and 22% (P=0.10) and patient survival rate was 81% and 76% (P=0.20) in patients with complete recovery from AKI and patients without recovery, respectively. Patients with completely recovered AKI had similar risk-adjusted long-term mortality compared with patients who did not recover (hazard ratio [95% confidence interval]=1.42 [1.15-2.05] versus 1.53 [1.01-2.00]). CONCLUSIONS: Patients who recover completely from early AKI after lung transplantation have a similar risk for CKD and long-term mortality compared with patients who do not recover.


Subject(s)
Acute Kidney Injury/therapy , Lung Transplantation/adverse effects , Postoperative Complications/mortality , Recovery of Function , Acute Kidney Injury/mortality , Adult , Amidohydrolases/blood , Female , Follow-Up Studies , Hospital Mortality , Humans , Incidence , Lung Transplantation/mortality , Male , Middle Aged , Morbidity , Renal Insufficiency, Chronic/mortality , Retrospective Studies , Risk Factors
10.
J Heart Lung Transplant ; 31(3): 244-51, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21996350

ABSTRACT

BACKGROUND: The effect of acute kidney injury (AKI) after lung transplantation has been described infrequently and with inconsistent results. Using a newly adopted and validated definition of AKI proposed by the Acute Kidney Injury Network (AKIN), we examined the incidence of AKI and associated renal morbidity and short-term and long-term mortality. METHODS: We retrospectively evaluated data of 657 patients who underwent lung transplantation from 1997 to 2009. Outcomes analyzed were the incidence of AKI, as defined and categorized into 3 stages according to creatinine criteria from the AKIN classification (AKIN 1, AKIN 2, and AKIN 3), cumulative incidence of chronic kidney disease (CKD), as defined by an estimated glomerular filtration rate ≤ 29 ml/min/1.73 m(2), and/or the onset of end-stage renal disease, as defined by the need for renal replacement therapy for 8 weeks with no recovery on follow-up or need for kidney transplant, and long-term mortality. RESULTS: We identified 424 patients (65%) who had at least 1 AKI (309 [47%] AKIN 1 and 115 [17%] AKIN 2-3) event in the first 2 weeks after transplantation. At 1 year, the cumulative incidence of CKD was 5.8%, 12.8%, 24.5 % in the no-AKI, AKIN 1, and AKIN 2-3 patients, respectively. After a median follow-up of 2.2 years, 277 (42%) died. One-year patient survival was 91%, 82%, 66% in the no-AKI, AKIN 1, and AKIN 2-3 patients, respectively. Adjusting for age, sex, race, type and cause of lung transplant, diabetes, and hypertension, the hazard ratio for death was 1.7 (95% confidence interval, 1.2-2.2; p = 0.0002) for AKIN 1 and 2.9 (95% confidence interval, 1.7-3.7; p < 0.001) for AKIN 2-3. CONCLUSIONS: AKI is a common complication after lung transplantation and is associated with increased risk of CKD and all cause-mortality on long-term follow-up.


Subject(s)
Acute Kidney Injury/epidemiology , Acute Kidney Injury/mortality , Lung Transplantation , Postoperative Complications , Acute Kidney Injury/classification , Adult , Aged , Creatinine/blood , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate
11.
Transplantation ; 91(12): 1424-35, 2011 Jun 27.
Article in English | MEDLINE | ID: mdl-21516067

ABSTRACT

BACKGROUND: In many healthcare contexts, evidence exists that patients who participate in research protocols (PRP) significantly differ from nonparticipants. These differences may affect the external validity of study findings, reflect access to care, and potentially explain sources of difference in patient outcomes. There is no comprehensive study evaluating PRP among transplant recipients. METHODS: We evaluated the national Scientific Registry of Transplant Recipients from 2000 to 2008 for liver, kidney, heart, lung, and simultaneous pancreas/kidney transplant recipients in the United States for which PRP for immunosuppressive medications is reported at follow-up. Our primary aims were to evaluate participant characteristics, compare outcomes between participants and nonparticipants, and assess variability of PRP between centers and medications. RESULTS: The national proportions of PRP at 1 year by organ were kidney (8.2%), liver (2.9%), heart (5.0%), lung (2.6%), and simultaneous pancreas/kidney (2.8%). Factors associated with PRP included recipients' educational attainment, insurance, race/ethnicity, gender and age, donor age, transplant number, income, distance to center, and center volume. Graft and patient survivals were significantly higher among PRP for kidney, liver, and lung transplant recipients. PRP varied markedly between centers (range, 0%-58%) and by immunosuppressant medications. CONCLUSIONS: There are systematic differences between participants and nonparticipants in research in the transplant population that may affect the external validity of research findings. Superior outcomes among participants may suggest that participation in research itself affords certain benefits. Future research evaluating the mechanisms for differential participation rates and improved survival among participants is needed.


Subject(s)
Organ Transplantation/methods , Patient Participation , Adolescent , Adult , Aged , Biomedical Research/organization & administration , Female , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Registries , Reproducibility of Results , Tissue and Organ Procurement/methods , United States
12.
Transplantation ; 90(12): 1486-92, 2010 Dec 27.
Article in English | MEDLINE | ID: mdl-21042239

ABSTRACT

BACKGROUND: We report our initial experience in using the proteasome inhibitor, bortezomib, to treat established antibody-mediated rejection (AMR) in 20 patients. METHODS: There were 16 kidney-only and 4 kidney-combined organ recipients with de novo donor-specific antibody (DSA) and histologic evidence of AMR with peritubular capillaries C4d deposition. AMR was diagnosed 19.8 months (range 1-71 months) posttransplant. Patients received intravenous corticosteroids followed by a 2-week cycle on days 1-4-8-11 of plasmapheresis and 1.3 mg/m² bortezomib; then 0.5 mg/kg intravenous immunoglobulin four times. RESULTS: De novo class I DSA was detected in 11 (55%) and class II DSA in 18 (90%) recipients. The absolute mean difference between peak-nadir dominant DSA was 68,171 molecules of equivalent soluble fluorochrome (P<0.0001), representing 55%±22%. Only two patients (10%) had undetectable DSA after treatment. Patient survival is 100%, and graft survival is 85% with a mean follow-up of 9.8 months (range 2-20 months). The treatment was generally well tolerated but caused fatigue, gastrointestinal complaints, fluid retention, and thrombocytopenia in a number of patients. The last follow-up estimated glomerular filtration rate was 41.9±16.8 mL/min (range 20.6-72.2 mL/min). However, only 25% returned to their baseline renal function before AMR, and many have proteinuria with urine protein/creatinine more than 0.5 in 41% and more than 1.0 in 18%. CONCLUSIONS: The bortezomib-containing regimen demonstrated activity in AMR but seems to be most effective before the onset of significant renal dysfunction (serum creatinine <3 mg/dL) or proteinuria (<1 g/day). The best use of bortezomib to treat AMR should be evaluated in controlled trials using dosing strategies that include longer courses or retreatment schedules.


Subject(s)
Boronic Acids/therapeutic use , Graft Rejection/drug therapy , Isoantibodies/immunology , Kidney Transplantation/immunology , Protease Inhibitors/therapeutic use , Proteasome Inhibitors , Pyrazines/therapeutic use , Actuarial Analysis , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Antibody Specificity , Bortezomib , Combined Modality Therapy , Creatinine/blood , Female , Graft Rejection/immunology , Graft Survival/physiology , Humans , Kidney Transplantation/mortality , Liver Transplantation/immunology , Male , Middle Aged , Pancreas Transplantation/immunology , Plasmapheresis
13.
Clin J Am Soc Nephrol ; 5(10): 1881-6, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20813856

ABSTRACT

BACKGROUND AND OBJECTIVES: ESRD has an adverse impact on patients who have had previous nonrenal solid-organ transplants (NRTxs; liver, heart, lung) and may be referred for a kidney transplant (KTx). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using Scientific Registry of Transplant Recipients data for all KTx candidates who had NRTx and were listed between 1995 and 2008, incidence of NRTx listings were compared with trends in KTx without NRTX. The efficacy of kidney transplantation relative to dialysis was measured in time-dependent Cox models that incorporated candidates with the applicable previous organ transplant as a reference group. RESULTS: Overall, 4904 NRTx candidates were listed during the study period, growing from <1% of candidates before 1995 to 3.3% in 2008. A total of 38% of NRTx candidates were listed preemptively versus 21% of other candidates. NRTx candidates had dramatically shorter half-lives (≤ 4 years) after listing compared with previous KTx recipients (9.2 years). KTx demonstrated a survival advantage for each type of NRTx candidate relative to maintenance dialysis. Listing for expanded-criteria donor kidneys averaged 47% and did not differ significantly by previous transplant category. CONCLUSIONS: KTx candidates who are placed on the waiting list after NRTx constitute a significant and more rapidly growing cohort compared with the general KTx candidate population. NRTx candidates are frequently listed preemptively but have rapid decline once placed on the waiting list. Targeted use of expanded-criteria donor and living-donor transplants in the NRTx population may be particularly important given their high mortality on the waiting list.


Subject(s)
Heart Transplantation/adverse effects , Kidney Failure, Chronic/therapy , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Lung Transplantation/adverse effects , Renal Dialysis/adverse effects , Waiting Lists , Adult , Female , Heart Transplantation/mortality , Humans , Kaplan-Meier Estimate , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Liver Transplantation/mortality , Logistic Models , Lung Transplantation/mortality , Male , Middle Aged , Odds Ratio , Proportional Hazards Models , Registries , Renal Dialysis/mortality , Risk Assessment , Risk Factors , Time Factors , United States , Waiting Lists/mortality
14.
Med Care ; 48(10): 907-14, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20733532

ABSTRACT

BACKGROUND: Transplant center performance evaluations have garnered substantial attention in recent years. Among sources of bias that may affect measured performance are underlying characteristics of donor organs. An unresolved question is whether centers accepting higher-risk donations are placed in jeopardy for lower evaluations independent of actual quality of care. OBJECTIVE: The primary aim was to assess whether unmeasured characteristics of donor organs impact risk-adjusted outcomes used for center performance evaluations. SUBJECTS: The study included adult kidney transplant recipients (n = 53,791) from 1994 to 2008 from a national registry. RESEARCH DESIGN: We compared adjusted graft survival with use of paired-donor kidneys (allocated to high- and low-performing centers) and unpaired donor kidneys to investigate whether measured center performance was consistent with organs derived from the same donor (minimizing the influence of noncodified risk factors). RESULTS: The primary finding was that differences between centers were unaffected by use of paired or unpaired donations (hazard ratio for patients transplanted at high performing centers with paired kidneys = 0.63 [95% CI, 0.53-0.74] and with unpaired kidneys = 0.66 [95% CI, 0.62-0.70], P value for interaction = 0.52). This finding was consistent over 5 consecutive cohorts, based on either concurrent or prospective outcomes and by altering the threshold criteria for identification of performance outliers. CONCLUSIONS: Results indicate that underlying selection bias from donor characteristics does not impact transplant center evaluations. This is important evidence that donor selection is not a primary driver for evaluated quality of care among transplant centers and acceptance of higher-risk kidneys should not be perceived as a primary threat to measured performance.


Subject(s)
Donor Selection/standards , Kidney Transplantation/standards , Tissue Donors/statistics & numerical data , Tissue and Organ Procurement/standards , Adult , Aged , Donor Selection/statistics & numerical data , Female , Health Facilities/standards , Health Facility Administration , Humans , Kidney Transplantation/statistics & numerical data , Male , Middle Aged , Outcome Assessment, Health Care/statistics & numerical data , Selection Bias , United States/epidemiology
15.
Transplantation ; 90(4): 419-26, 2010 Aug 27.
Article in English | MEDLINE | ID: mdl-20683281

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) viremia that is resistant or refractory to the standard antiviral therapy still constitutes a major threat to high-risk transplant recipients. In addition, multiple CMV recurrences may lead to neutropenia because of repeated courses of therapy with ganciclovir derivatives. Leflunomide, a drug for rheumatoid arthritis, has been reported to have anti-CMV activity. This study reports on its use in 17 transplant recipients with complex CMV syndromes who had failed or were intolerant to other therapies. METHODS: Single-center, retrospective study. Clinical data were extracted from the electronic medical record. CMV DNA viral loads were performed by quantitative hybrid capture assay. RESULTS: Leflunomide was initiated after a median of three episodes of CMV viremia, with a mean peak viral load of 245,826 copies/mL. Initial clearance of CMV viremia was observed in 14 of 17 patients (82%), and 9 of 17 (53%) patients achieved a long-term suppression of CMV recurrences. Higher peak viral load and higher viral load at the start of leflunomide therapy were associated with failure to suppress viremia. The duration of leflunomide therapy ranged from 1 to 24 months (median 3.5 months, interquartile range 2.6-7 months), and the mean time to an undetectable CMV-DNA was 1.9 months. Adverse effects included diarrhea (35%), anemia (18%), and increased liver function tests (12%). CONCLUSIONS: Leflunomide, alone or in combination, has potential utility in treatment of complex CMV syndromes and in long-term suppression of viremia. The optimal duration of therapy and the balance of risks and benefits are not yet known.


Subject(s)
Antiviral Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Isoxazoles/therapeutic use , Cytomegalovirus Infections/diagnosis , Ganciclovir/therapeutic use , Heart Transplantation , Humans , Immunosuppressive Agents/therapeutic use , Leflunomide , Lung Transplantation , Off-Label Use , Organ Transplantation , Retrospective Studies , Risk Assessment , Viral Load
16.
J Heart Lung Transplant ; 28(6): 564-71, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19481016

ABSTRACT

BACKGROUND: Improvement in renal function has been noted in some lung allograft recipients with chronic kidney disease (CKD) converted from a calcineurin inhibitor (CNI)- to a sirolimus (SRL)-based immunosuppressive regimen. However, not all patients have such a positive response. We sought to investigate independent predictors of a favorable renal response in a cohort of lung transplant recipients. METHODS: We retrospectively studied 56 lung transplant recipients with CKD, defined as a pre-conversion estimated glomerular filtration rate (eGFR) < or =60 ml/min/1.73 m(2), who had been converted to CNI-sparing regimens using SRL (CNI-free: n = 10; CNI dose reduction + SRL: n = 46). Proteinuria prior to conversion, defined as > or =1(+) on urine dipstick, was determined when available (n = 51). Changes in mean eGFR post-conversion and independent predictors of a favorable renal response, defined as a rise in eGFR > or =20% within 1 month, were investigated. RESULTS: Mean eGFR at conversion was 35 +/- 14 ml/min/1.73 m(2), increasing by 8 +/- 14 ml/min/1.73 m(2) (p < 0.01) by 1 month post-conversion, a trend that remained significant out to 18 months. A total of 43% (n = 24) of patients had a rise in eGFR > or =20%. Forced expiratory volume in 1 second (FEV(1)) remained stable in survivors maintained on SRL and only 1 rejection episode occurred. When controlling for gender, age, pre-conversion eGFR and CNI-free vs CNI-dose reduction, the only variable that remained independently predictive of a favorable renal response was absence of proteinuria, with an odds ratio = 3.3 (95% confidence interval 1.0 to 12.5, p = 0.05). CONCLUSIONS: Non-proteinuric lung transplant survivors with CKD are more likely to respond favorably from a renal standpoint after conversion to SRL with CNI-dose reduction or elimination.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Diseases/physiopathology , Kidney/physiopathology , Lung Transplantation/immunology , Proteinuria/prevention & control , Sirolimus/therapeutic use , Adult , Aged , Calcineurin Inhibitors , Chronic Disease , Cohort Studies , Female , Glomerular Filtration Rate/physiology , Humans , Immunosuppressive Agents/adverse effects , Kidney Diseases/complications , Male , Middle Aged , Predictive Value of Tests , Proteinuria/diagnosis , Proteinuria/etiology , Retrospective Studies , Sirolimus/adverse effects , Treatment Outcome
17.
Kidney Int ; 75(10): 1079-87, 2009 May.
Article in English | MEDLINE | ID: mdl-19212414

ABSTRACT

Due to the shortage of organs, living donor acceptance criteria are becoming less stringent. An accurate determination of the glomerular filtration rate (GFR) is critical in the evaluation of living kidney donors and a value exceeding 80 ml/min per 1.73 m(2) is usually considered suitable. To improve strategies for kidney donor screening, an understanding of factors that affect GFR is needed. Here we studied the relationships between donor GFR measured by (125)I-iothalamate clearances (mGFR) and age, gender, race, and decade of care in living kidney donors evaluated at the Cleveland Clinic from 1972 to 2005. We report the normal reference ranges for 1057 prospective donors (56% female, 11% African American). Females had slightly higher mGFR than males after adjustment for body surface area, but there were no differences due to race. The lower limit of normal for donors (5th percentile) was less than 80 ml/min per 1.73 m(2) for females over age 45 and for males over age 40. We found a significant doubling in the rate of GFR decline in donors over age 45 as compared to younger donors. The age of the donors and body mass index increased over time, but their mGFR, adjusted for body surface area, significantly declined by 1.49+/-0.61 ml/min per 1.73 m(2) per decade of testing. Our study shows that age and gender are important factors determining normal GFR in living kidney donors.


Subject(s)
Glomerular Filtration Rate , Kidney Transplantation/standards , Living Donors , Adult , Black or African American , Age Factors , Female , Humans , Living Donors/supply & distribution , Male , Middle Aged , Reference Values , Sex Factors , White People
18.
Transplantation ; 86(2): 223-30, 2008 Jul 27.
Article in English | MEDLINE | ID: mdl-18645483

ABSTRACT

BACKGROUND: Accurate determination of kidney function is critical in the evaluation of living kidney donors and higher donor glomerular filtration rate (GFR) is associated with better allograft outcomes. However, among transplant centers donor kidney function evaluation varies widely. METHODS: The performance of creatinine clearance (CrCl), Modification of Diet in Renal Disease (MDRD), the re-expressed MDRD equations with standardized creatinine, and the Cockcroft-Gault (CG) formula as compared with (125)I-iothalamate GFR (iGFR) was analyzed in 423 donors. All methods of GFR measurement were then evaluated for their association with graft function at 1 year. RESULTS: The MDRD and re-expressed MDRD equations underestimated iGFR whereas CG showed minimal bias (median difference=-11.0, -16.3, and -0.5 mL/min/1.73 m(2), respectively). CrCl overestimated iGFR (10 mL/min/1.73 m(2)). The MDRD, re-expressed MDRD, and CG formulas were more accurate (88%, 86%, and 88% of estimates within 30% of iGFR, respectively) than CrCl (80% within 30% of iGFR). Interestingly, low bias and high accuracy were achieved by averaging the MDRD estimation with the CrCl result; both methods available to the clinician in most transplant centers. We also showed that predonation GFR as measured by isotopic renal clearance or any of the creatinine-based estimation formulas may be associated with allograft function at 1 year, whereas the widely used CrCl was not. CONCLUSIONS: Variable performance was seen among different GFR estimations, with CrCl being the poorest. Recent recommendations to use the MDRD equation with standardized serum creatinine did not improve its performance. However, recognizing the limited availability of GFR laboratories, these methods are still clinically useful if used with caution and understanding their limitations.


Subject(s)
Creatinine/blood , Creatinine/urine , Glomerular Filtration Rate , Kidney Transplantation/methods , Adult , Cohort Studies , Female , Humans , Kidney Function Tests , Living Donors , Male , Middle Aged , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Treatment Outcome
19.
Transplantation ; 83(5): 593-9, 2007 Mar 15.
Article in English | MEDLINE | ID: mdl-17353780

ABSTRACT

Living donor renal allograft survival is superior to that achieved from deceased donors, although graft outcome is suboptimal in some of these patients. In an effort to identify the subset of patients at high risk for poor outcomes we studied donor risk factors in 248 living kidney donor-recipient pairs. Unadjusted donor (125)I-iothalamate GFR (iGFR), donor age more than 45 years, donor total cholesterol level less than 200 mg/dL, and donor systolic blood pressure (SBP) less than 120 mm Hg were correlated with allograft estimated glomerular filtration rate (eGFR), and incidence of acute rejection (AR), delayed graft function and/or graft loss at 2 years posttransplantation. Donor iGFR less than 110 mL/min (slope=-7.40, P<0.01), donors more than 45 years (slope=-8.76, P<0.01), donor total cholesterol levels more than 200 mg/dL (slope=-10.03, P<0.01), and SBP more than 120 mm Hg (slope=-5.60, P=0.03) were associated with lower eGFR. By multivariable linear regression analysis these variables remained independently associated with lower eGFR, and poorer outcomes. The increasing number of donor factors (age, iGFR, cholesterol, and blood pressure) was directly associated with worse posttransplant eGFR (P<0.01). In conclusion, our data suggest that routine assessment of living donor parameters could supplement the consideration of recipient characteristics in predicting posttransplant risk of graft injury/dysfunction.


Subject(s)
Kidney Transplantation/physiology , Living Donors/classification , Treatment Outcome , Acute Disease , Adult , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Blood Pressure , Cholesterol/blood , Family , Female , Glomerular Filtration Rate , Graft Rejection/epidemiology , Humans , Kidney Transplantation/mortality , Living Donors/statistics & numerical data , Male , Middle Aged , Multivariate Analysis , Reoperation/statistics & numerical data , Retrospective Studies , Survival Analysis , Time Factors , Transplantation, Homologous
20.
Transplantation ; 82(3): 368-74, 2006 Aug 15.
Article in English | MEDLINE | ID: mdl-16906035

ABSTRACT

BACKGROUND: Calcineurin inhibitor(CNI)-free protocols using sirolimus (SRL) in kidney transplantation have proven effective, although reports have linked SRL to proteinuria. We sought to investigate this link and its impact on graft function. METHODS: We retrospectively analyzed 184 live donor kidney transplant recipients who exclusively received de novo CNI-based (n = 106) or SRL-based (n = 78) regimens. Estimated glomerular filtration rate (GFR) and semi-quantitative dipstick proteinuria measurements were obtained at one, six, 12, and 24 months and six and 12 months, respectively. RESULTS: SRL-treated patients had higher frequencies of proteinuria (> or =1+) at 6 months (40.8% vs. 21.4%, P = 0.006) and 12 months (37.8% vs. 18.4%, P = 0.004) than those treated with CNI. Independent predictors of proteinuria at 12 months were GFR at one month (OR 0.62 per 10 ml/min/1.73 m, P<0.001), delayed graft function (OR 11.5, P = 0.02), and a SRL-based regimen (OR 4.18, P=0.002). By univariable analysis, SRL vs. CNI patients had higher GFR at each point. SRL-treated patients without proteinuria had higher GFR at 12 months compared to CNI-treated patients with and without proteinuria (66 vs. 50 or 56 ml/min/1.73 m, P < 0.05). No difference in GFR was seen between SRL-treated patients with proteinuria vs. CNI-treated patients without proteinuria (57 vs. 56 ml/min/1.73 m, P > 0.05). Absence of proteinuria and a SRL-based regimen remained independently associated FS with higher GFR at 12 months by multivariable analyses. CONCLUSIONS: De novo SRL-based immunosuppression is associated with a higher frequency of semi-quantitative proteinuria, however, estimated graft function at 1 year posttransplant remains superior to that of CNI-treated patients. Nevertheless, the long-term implications of these findings need to be determined.


Subject(s)
Calcineurin Inhibitors , Graft Survival/immunology , Immunosuppressive Agents/pharmacology , Kidney Transplantation , Living Donors , Proteinuria/urine , Sirolimus/pharmacology , Adult , Calcineurin/metabolism , Female , Follow-Up Studies , Humans , Kidney/physiology , Male , Middle Aged
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