Long-term Deterioration Of Renal Function Research Articles

Predictors of renal function deterioration at one year after off-clamp non-renorrhaphy partial nephrectomy.

Preservation of renal function is an important goal in renal cell carcinoma-related surgery. Although several case-dependent techniques for renal pedicle clamping and hemostasis have been used, their effects on long-term renal function are controversial. The clinical records of 114 patients who underwent off-clamp non-renorrhaphy open partial nephrectomy at our hospital were retrospectively reviewed. Perioperative estimated glomerular filtration rate (eGFR) preservation was calculated, and predictors of eGFR decline 12 months post-surgery and overtime deterioration of renal function were identified using a multivariate regression analysis. The median patient age was 65 years, and the median tumor size was 27 mm. The mean eGFR preservation at 1, 3, and 12 months post-surgery were 90.1%, 89.0%, and 86.9%, respectively. eGFR decline at 1 and 3 months were associated with poor eGFR preservation at 12 months with the odds ratio (95% confidence interval (CI)) of 1.97 and 3.157, respectively. Multivariate regression analyses revealed that tumor size was an independent predictor of eGFR decline at 12 months. Among 65 patients with eGFR preservation over 90% at 1 month post-surgery, eGFR value of 28 patients deteriorated below 90% at 12 months post-surgery compared with preoperative eGFR. Tumor size and eGFR preservation at 1 month were independent predictors of long-term renal function deterioration. Tumor size predicted eGFR decline 12 months post-surgery. Only a mild decline in eGFR was observed between 3 and 12 months after open partial nephrectomy. Tumor size and eGFR preservation at 1 month predicted the deterioration of renal function over time.

Nephrological management and drug dosing in patients with rheumatic diseases and renal insufficiency

In patients with inflammatory rheumatic diseases and renal insufficiency there are two challenges for physicians: to adapt the antirheumatic medication to the renal function and to carry out anephroprotective treatment that prevents long-term deterioration of renal function and reduces the elevated cardiovascular risk. Aliterature search (in PubMed) was carried out and the current state of knowledge on nephroprotective treatment strategies and the treatment of rheumatic diseases in the presence of renal insufficiency was collated, evaluated and summarized. Lifestyle interventions, especially the cessation of smoking and drug treatment strategies form the basis of nephroprotection including the control of diabetes mellitus with metformin, sodium glucose transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1) analogues and control of hypertension with blockade of the renin-angiotensin-aldosterone system (RAAS), hyperlipidemia, hyperphosphatemia and metabolic acidosis. The SGLT2 inhibitors are also effective for nondiabetic nephropathy. The elevated cardiovascular risk is further reduced by effective control of inflammatory rheumatic activity. Numerous conventional disease modifying antirheumatic drugs, especially methotrexate and the Janus kinase (JAK) inhibitors baricitinib and filgotinib, must mostly be adapted to the renal function. In contrast, biologics can be given in standard doses with the exception of anakinra. The increased cardiovascular risk currently limits the use of tofacitinib in patients with renal insufficiency. The antirheumatic medication should be modified and acomplex nephroprotective treatment concept is mandatory in the management of patients with rheumatic disease and renal insufficiency, that in the best-case scenario can be guaranteed by a close interdisciplinary cooperation of rheumatologists and nephrologists.

Visit-to-visit variability in albuminuria predicts renal function deterioration in patients with type 2 diabetes.

Aims/IntroductionWe aimed to study the predictive ability of visit‐to‐visit variability in albuminuria for changes in renal function in patients with type 2 diabetes mellitus.Materials and MethodsThe cohort study was carried out in a single medical center. In the model development cohort of 1008 subjects, we developed the albuminuria variability score (AVS) to evaluate the visit‐to‐visit variability in albuminuria, which was the percentage of the number of changes in the urine albumin : creatinine ratio ≥3.39 mg/mmol among all visit‐to‐visit urine albumin : creatinine ratio differences within an individual. Multivariate logistic regression was applied to predict the influence of AVS levels on the occurrence of study end‐points. In another independent validation cohort of 310 participants, survival analysis was carried out to evaluate the ability of AVS in predicting the study end‐point.ResultsIn the model development cohort, a higher AVS was associated with higher adjusted odds of having a declined or rapidly declined estimated glomerular filtration rate (eGFR) trajectory (1.84, 95% confidence interval 1.23–2.76 and 5.70, 95% confidence interval 2.28–14.25, respectively), a resultant eGFR <60 mL/min/1.73 m2 (2.61, 95% confidence interval 1.63–4.16) and a >40% decline in eGFR from baseline (6.44, 95% confidence interval 2.15–19.26). In the validation cohort, a higher AVS independently predicted a 5‐year decrease of >40% in eGFR to <60 mL/min/1.73 m2 (adjusted hazard ratio 3.33, 95% confidence interval 1.10–10.05). Integrated discrimination index and concordance statistics showed that AVS significantly improved the predictive ability of the models.ConclusionsVisit‐to‐visit variability in albuminuria can independently predict long‐term renal function deterioration in patients with type 2 diabetes mellitus. Further investigations are warranted to elucidate the potential clinical applications.

Influence of Robot-Assisted Partial Nephrectomy on Long-Term Renal Function as Assessed Using 99m-Tc DTPA Renal Scintigraphy.

Background: The long-term split renal function after robot-assisted partial nephrectomy (RAPN) is yet to be elucidated. This study aimed to assess long-term renal function of RAPN, using renal scintigraphy, and to identify clinical factors related to deterioration of renal function on the affected side of the kidney. Patients and Methods: RAPN for small tumors was performed, and split renal function was evaluated using 99m-Tc DTPA renal scintigraphy before and 1 year after surgery. Clinical factors (age, gender, body mass index, tumor side, presence of urinary protein, diabetes, hypertension, and dyslipidemia), perioperative factors (renal nephrectomy score [RNS], tumor diameter, overall surgery duration, console time, warm ischemic time, and amount of bleeding), and renal function (estimated glomerular filtration rate [eGFR] and glomerular filtration rate [GFR] measured using scintigraphy on both the affected and contralateral kidneys) were analyzed. Results: Sixty-six patients were included in the study. The median eGFR decreased from 71.9 to 63.9 mL/min after 1 year (p < 0.001), accounting for a mean loss of 10.1%. In scintigraphy examination, the median GFR on the affected kidney side decreased from 41.1 to 33.7 mL/min after 1 year (p < 0.001), accounting for a mean loss of 16.8%. RNS was significantly associated with renal function. Among RNS factors, the N factor is associated with renal function after RAPN. Conclusion: RNS, particularly the N factor, possibly influences the long-term deterioration of renal function after RAPN.

Incidence and Predictors of Long-Term Renal Function Deterioration after Implantation of a Centrifugal, Continuous-Flow Device for Bridge to Transplant

Purpose Severe heart failure patients often have renal dysfunction (RD) due to low cardiac output. Especially in Japan, left ventricular assist device (LVAD) patients as bridge to transplantation need to wait for cardiac transplant for a long time due to limited donors. The aim of this study was to identify the long-term changes of renal function after implantation of an EVAHEART® which is a centrifugal-type, continuous-flow LVAD, and factors predictive of renal function deterioration. Methods This study was a retrospective observational cohort study. EVAHEART® (LVAD) implantation was performed in 44 patients as a BTT at our institute between May 2005 and 2018. We investigated changes in renal function over 2 years among 41 patients supported by EVAHEART® over 6 months. Furthermore, we also investigated the predictive factors of worsening renal failure. Results The patients’ mean age at LVAD implantation was 40 ± 12 years; 35 were male. Mean ejection fraction was 20 ± 6 %. Mean estimated glomerular filtration rate (eGFR) at LVAD implantation was 66 ± 31 ml/min/1.73m2; 20 (49 %) patients had renal impairment (eGFR Conclusion Renal function improved early after EVAHEART® implantation, but, gradually declined in most patients over 2 years. Among patients with renal impairment, high RA pressure, suggested “congestion”, at LVAD implantation had greater deterioration of renal function during a 2-year follow-up period.

Safety of left renal vein ligation during circular resection of the inferior vena cava in right-side kidney carcinoma with tumor venous thrombosis

Objective : to assess safety of left renal vein (LRV) ligation during circular resection of the inferior vena cava in right-side kidney carcinoma with tumor venous thrombosis. Materials and methods . We selected medical data of 63 renal cell carcinoma patients with tumor venous invasion undergone nephrectomy, thrombectomy, IVC resection with LRV ligation (Group 1; n = 29 (46.0 %)) or preservation of venous outflow from the contralateral kidney (Group 2; n = 34 (54.0 %)). Median age of study participants was 56.0 + 8.8 years (range: 32—72 years); a male to female ratio was 1:1.9. Such parameters as age, gender, median glomerular filtration rate (GFR), stages of chronic kidney disease (CKD), blood loss, and duration of surgery were comparable across the two groups ( р &gt;0.05 for all parameters). Median follow-up was 32.8 months (range: 1—226 months). Results. We observed no significant changes in median GFR in the late postoperative period compared to baseline among patients with ligated LRV (65.7 vs 71.2 mL/min/1.73 m2; р &gt;0.05) and patients with preserved venous outflow from the contralateral kidney (60.6 vs 68.4 mL/min/1.73 m2; р &gt;0.5). Patients that underwent LRV ligation were less likely to have reduced GFR compared to those with normal contralateral renal venous outflow (34.5 % vs 44.1 %; p &gt;0.05). However, participants with ligated LRV had CKD upstaging (from stage 0—I to stage I—II) more frequently than participants with preserved venous outflow (27.6 % vs 5.9 %; р = 0.022). None of the patients developed stage III CKD after LRV ligation. Conclusion . LRV ligation during circular resection of the IVC in right-side renal cell carcinoma patients with tumor venous thrombosis does not lead to a clinically significant decrease in long-term deterioration of renal function.

Impact of Aortic Wall Thrombus on Long-term Changes in Renal Function Among Patients Treated by Fenestrated-Branched Endografts for Complex Aortic Aneurysms

Renal function deterioration (RFD) is an important determinant of mortality in patients treated for complex aortic aneurysms. Catheter and guidewire manipulations in diseased aortas during fenestrated-branched endovascular aneurysm repair (F-BEVAR) have been associated with risk of emboli leading to loss of renal function. The aim of this study was to describe the impact of atherosclerotic wall thrombus (AWT) on long-term RFD in patients treated by F-BEVAR for pararenal and extent IV thoracoabdominal aortic aneurysms. Clinical data of 212 patients treated for complex aortic aneurysms with F-BEVAR were entered into a prospectively maintained database (2007-2015). AWT was evaluated by computed tomography angiography using volumetric measurements in nonaneurysmal aortic segments. AWT was classified as mild, moderate, or severe using a score system based on thrombus extent, type, thickness, area, and circumference. Patient survival and renal outcomes were assessed at dismissal, at 6 to 8 weeks, at 6 months, and annually, including serum creatinine concentration, estimated glomerular filtration rate (eGFR), chronic kidney stage, RIFLE (risk, injury, failure, loss of kidney function, end-stage renal disease) criteria, need for renal replacement therapy, and presence of kidney infarction. There were 169 male (80%) and 43 female (20%) patients with mean age of 75 ± 7 years. Aneurysm extent was pararenal in 157 patients and extent IV thoracoabdominal aortic aneurysm in 55. A total of 700 renal-mesenteric arteries were incorporated (3.1 ± 1 vessels/patient). AWT was classified as mild in 98 patients (46%), moderate in 75 patients (35%), and severe in 39 patients (19%). At 30 days, 45 patients (21%) developed RFD (>30% decline in eGFR). Decline in eGFR and kidney infarction were associated with higher AWT volume index and severe AWT classification (P < .05). There was no association of AWT with 30-day mortality, which was 0.5% for the entire cohort. Mean follow-up was 29 ± 23 months. Freedom from RFD was 73% ± 6% for mild, 81% ± 6% for moderate, and 66% ± 8% for severe AWT patients at 3 years (P = .012). Patient survival was 73% ± 5% for mild, 72% ± 6% for moderate, and 69% ± 10% for severe AWT patients at 3 years (P = .67). Severe AWT is a significant predictor of kidney infarction and early and late decline in renal function among patients treated by F-BEVAR. Severe AWT had no impact on early and late patient survival. Preoperative planning and decision-making should include careful assessment of AWT in patients with complex aortic aneurysms considered for F-BEVAR.

Novel biomarkers of acute kidney injury: Evaluation and evidence in urologic surgery.

Patients undergoing urologic surgery are at risk of acute kidney injury (AKI) and consequently long-term deterioration in renal function. AKI is further associated with significantly higher odds of perioperative complications, prolonged hospital stay, higher mortality and costs. Therefore, better awareness and detection of AKI, as well as identification of AKI determinants in the urological surgery setting is warranted to pre-empt and mitigate further deterioration of renal function in patients at special risk. New consensus criteria provide precise definitions of diagnosis and description of the severity of AKI. However, they rely on serum creatinine (SCr), which is known to be an inaccurate marker of early changes in renal function. Therefore, several new urinary and serum biomarkers promise to address the gap associated with the use of SCr. Novel biomarkers may complement SCr measurement or most likely improve the diagnostic accuracy of AKI when used in combinations. However, novel biomarkers have to prove their clinical applicability, accuracy, and cost effectiveness prior to implementation into clinical practice. Most preferably, novel biomarkers should help to positively improve a patient's long-term renal functional outcomes. The purpose of this review is to discuss currently available biomarkers and to review their clinical evidence within urologic surgery settings.

Emerging urinary markers of renal injury in obstructive nephropathy.

The effects of obstruction on renal function are the consequence of many factors that profoundly alter all components of glomerular function. Besides the acute effects on glomerular filtration rate and tubule function, a chronic obstruction induces tubular and interstitial injury that results from the activation of different pathways. The progression of tubulointerstitial injury leads to chronic renal damage characterized by tubular atrophy, inflammatory cell infiltration, and interstitial fibrosis. Obstructive nephropathy is an evolving disease in which the renal damage continues even after relief of the obstruction. In particular, it has been demonstrated that the time of relief is the most important factor in predicting long-term renal function deterioration. In this setting, the EGF/MCP-1 ratio, urinary NGAL, and urinary KIM-1 are useful early biomarkers of progressive renal damage and could have a potential role in predicting the long-term renal outcome. This minireview summarizes the role of these emerging urinary biomarkers of obstructive nephropathy based on the current understanding of the pathophysiology of renal injury.

Renal safety in patients treated with bisphosphonates for osteoporosis: A review

Bisphosphonates are widely used for the treatment of osteoporosis and are generally well tolerated. However, the United States Food and Drug Administration safety reports have highlighted the issue of renal safety in bisphosphonate-treated patients. All bisphosphonates carry labeled "warnings" or a contraindication for use in patients with severe renal impairment (creatinine clearance <30 or <35 mL/min). Data from pivotal trials and their extension studies of bisphosphonates approved for the management of osteoporosis were obtained via PubMed, and were reviewed with support from published articles available on PubMed. Renal safety analyses of pivotal trials of oral alendronate, risedronate, and ibandronate for postmenopausal osteoporosis showed no short-term or long-term effects on renal function. Transient postinfusion increases in serum creatinine have been reported in patients receiving intravenous ibandronate and zoledronic acid; however, studies showed that treatment with these agents did not result in long-term renal function deterioration in clinical trial patients with osteoporosis. All bisphosphonate therapies have "warnings" for use in patients with severe renal impairment. Clinical trial results have shown that even in elderly, frail, osteoporotic patients with renal impairment, intravenous bisphosphonate therapy administration in accordance with the prescribing information did not result in long-term renal function decline. Physicians should follow guidelines for bisphosphonate therapies administration at all times.

THU0299 Factors Associated with Long-Term Renal Function Deterioration in Lupus Nephritis Treated Initially with Combined Prednisolone and Mycophenolate Mofetil (MMF) or Tacrolimus (TAC)

ObjectivesTo study the risk factors for renal function decline in patients with lupus nephritis treated initially with combined steroid and MMF or Tac.MethodsData were extracted from a randomized controlled trial...

662 Relief more than 2 weeks after ureteral obstruction is a risk factor for long-term renal function deterioration

662 Relief more than 2 weeks after ureteral obstruction is a risk factor for long-term renal function deterioration

Dapagliflozin Does Not Impact Renal Function in Patients with Type 2 Diabetes

Treatment with dapagliflozin (DAPA) is not associated with an increased risk of acute renal toxicity or long-term deterioration of renal function in patients with type 2 diabetes mellitus (T2DM) according to the results of a pooled analysis of 12 studies [NCT00263276; NCT00972244; NCT00528372; NCT00736879; NCT00528879; NCT00855166; NCT00357370; NCT00680745; NCT00683878; NCT00673231; NCT00643851; NCT00859898].

Long-term Outcomes of Percutaneous Nephrolithotomy in Patients With Chronic Kidney Disease: A Single-center Experience

To present our long-term follow-up data from patients with kidney stones and chronic kidney disease to identify the factors that could help predict the likelihood of long-term deterioration in renal function. From January 2002 to July 2010, we performed 1117 percutaneous nephrolithotomy (PNL) procedures in 1051 patients. We retrospectively analyzed 69 PNL procedures for 67 patients (47 men and 20 women) in whom the estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m(2). Two outcomes were measured. The percentage of change in the eGFR was measured comparing the preoperative and postoperative values. A 5% change in renal function was arbitrarily chosen to divide the population into 3 groups: group 1, an eGFR change of ≤ 5%; group 2, an eGFR increase of >5%; and group 3, an eGFR decrease of <5%. The second outcome measure was the presence of chronic kidney disease progressing in the first and consecutive years. The mean patient age was 57 ± 14.1 years. The complication rate was 23.1% using the Clavien classification. The mean follow-up time was 45.7 ± 17.08 months. The mean eGFR before and after PNL was 37.9 ± 14.05 and 45.1 ± 16.8, respectively. Diabetes mellitus (odds ratio 15.82, P = .036) and urinary infection (odds ratio 10.6, P = .04) were predictive of renal function deterioration at 1 year on multivariate analysis. PNL in patients with chronic kidney disease is safe and results in renal function preservation for a 5-year period. Diabetes mellitus and urinary infection were independent predictive of renal function impairment. Therefore, patients with diabetes mellitus and urinary tract infection should be followed up carefully and informed about hazardous potential of those diseases.

Vimentin Expression and Myofibroblast Infiltration Are Early Markers of Renal Dysfunction in Kidney Transplantation: An Early Stage of Chronic Allograft Dysfunction?

Introduction The objective of this study was to show the morphologic characteristics of allograft renal biopsies in renal transplant patients with stable renal function, which can potentially be early markers of allograft dysfunction, after 5 years of follow-up. Methods Forty-nine renal transplant patients with stable renal function were submitted to renal biopsies and simultaneous measurement of serum creatinine (Cr). Histology was evaluated using Banff scores, determination of interstitial fibrosis by Sirius red staining and immunohistochemical study of proximal tubule and interstitial compartment (using cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated according to the presence or absence of the epitheliomesenchymal transition (EMT). The interstitial presence of myofibroblasts and tubular presence of vimentin was also analyzed simultaneously. Renal function was measured over the follow-up period to estimate the reduction of graft function. Results Median posttransplant time at enrollment was 105 days. Patients were followed for 64.3 ± 8.5 months. The mean Cr at biopsy time was 1.44 ± 0.33 mg/dL, and after the follow-up it was 1.29 ± 0.27 mg/dL. Nine patients (19%) had a reduction of their graft function. Eleven biopsies (22%) had tubulointerstitial alterations according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen biopsies (32%) had high interstitial expression of myofibroblasts and tubular vimentin. Using Cox multivariate analysis, HLA and high expression of interstitial myofibroblasts and tubular vimentin were associated with reduction of graft function, yielding a risk of 3.3 ( P = .033) and 9.8 ( P = .015), respectively. Conclusion Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration.

Pre-emptive liver transplantation for primary hyperoxaluria (PH-I) arrests long-term renal function deterioration

Primary hyperoxaluria-I (PH-I) is a serious metabolic disease resulting in end-stage renal disease. Pre-emptive liver transplantation (PLT) for PH-I is an option for children with early diagnosis. There is still little information on its effect on long-term renal function in this situation. Long-term assessment of renal function was conducted using Schwartz's formula (estimated glomerular filtration rate-eGFR) in four children (Group A) undergoing PLT between 2002 and 2008, and a comparison was done with eight gender- and sex-matched controls (Group B) having liver transplantation for other indications. All patients received a liver graft from a deceased donor. Median follow-up for the two groups was 64 and 94 months, respectively. One child in Group A underwent re-transplantation due to hepatic artery thrombosis, while acute rejection was seen in one. A significant difference was seen in eGFR at transplant (81 vs 148 mL/min/1.73 m(2)) with greater functional impairment seen in the study population. In Group A, renal function reduced by 21 and 11% compared with 37 and 35% in Group B at 12 and 24 months, respectively. At 2 years post-transplantation, there was no significant difference in eGFR between the two groups (72 vs 100 mL/min/1.73 m(2), respectively; P = 0.06). Renal function remains relatively stable following pre-emptive LTx for PH-I. With early diagnosis of PH-I, isolated liver transplantation may prevent progression to end-stage renal disease and the need for renal transplantation.

Long-Term Graft Outcomes After Steroid Withdrawal in African American Kidney Transplant Recipients Receiving Sirolimus and Tacrolimus

We previously reported excellent short-term outcomes in African American kidney transplant patients receiving tacrolimus/sirolimus and withdrawn from corticosteroid therapy three months after transplantation. We now report the long-term outcomes of patients subjected to this protocol. In all, 47 African American kidney transplant recipients were enrolled in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids, without antibody induction therapy. Eligible patients were withdrawn from prednisone between three and five months posttransplant, and followed for acute rejection and changes in renal function. Outcomes (group 1, n=32) were compared to those of patients deemed not to be candidates for steroid withdrawal (group 2, n=15). After a mean follow-up of 48.5 months, 13 of 32 patients (41%) in group 1 developed acute rejection; only 13 patients (41%) remain steroid-free. Nine of 13 rejection episodes were associated with noncompliance. Graft loss occurred in 8 of 32 patients (25%) in group 1 and in 5 of 15 patients (33%) in group 2 (P=NS). Serum creatinine rose from 1.4+/-0.41 to 2.45+/-1.7 mg/dL in group 1 (P=0.004) and from 2.1+/-0.45 to 2.62+/-1.2 mg/dL (P=NS) in group 2. Among 13 patients in group 1 who remain steroid-free, creatinine concentration has risen from 1.28+/-.0.37 prior to steroid withdrawal to 1.64+0.54 at last follow-up (P=0.027). Late noncompliance and/or rejection in African Americans withdrawn from steroids have a negative impact on long-term graft function and survival. Steroid withdrawal may be associated with long-term deterioration of renal function, even in the absence of overt acute rejection.

Long-Term Benefit of Mycophenolate Mofetil in Renal Transplantation

The results of clinical trials of mycophenolate mofetil (MMF) and the analysis of numerous data from renal transplant registries have shown that MMF reduces the incidence of early and late rejection (even in the black population), is protective against long-term deterioration of renal function, and reduces late renal allograft loss independently of acute rejection without increasing the risk for malignancies.

Study 2: steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus: analysis of renal function beyond 1 year

S teroid withdrawal in African American kidney transplant recipients has traditionally resulted in high rates of acute rejection. Conversely, we have previously reported excellent short-term outcomes among 30 African Americans withdrawn from prednisone between 3 and 5 months after primary kidney transplantation and maintained on a regimen of concentration-controlled doses of sirolimus (SRL) (target trough concentrations, 10-15 ng/mL) and tacrolimus (TAC) (target trough concentrations, 5-8 ng/ mL). After a mean follow-up of 14 months, only 2 of 30 patients (6.7%) experienced biopsy-proven acute rejection and 90% of patients remained steroid-free. This cohort of patients has now been followed up for 12 to 35 months (mean, 24 7 months). Acute rejection, prompting renewal of steroid therapy, has occurred in 4 patients (13%), including episodes in 2 patients occurring at 15 and 16 months, respectively, after steroid withdrawal. Two of the 4 episodes of acute rejection occurred in the setting of prolonged delayed graft function and were discovered on “protocol” biopsies. The other 2 episodes were related to gross noncompliance. There has been a single graft loss and no deaths (97% graft survival, 100% patient survival). Prednisone was renewed for medical reasons unrelated to rejection in 2 other patients, including 1 with a late case of hemolytic uremic syndrome and another with intractable bone pain prompting discontinuation of TAC. At last follow-up, 24 of 30 patients (80%) remained steroid-free. For the cohort of 29 patients with functioning grafts, serum creatinine concentration increased from 1.4 0.44 mg/dL before steroid withdrawal to 2.2 1.8 mg/dL at last follow-up (P .028). For the 24 patients who remain off prednisone and free of clinically overt acute rejection, serum creatinine concentration has increased from 1.44 0.4 to 1.65 0.4 mg/dL (P .006). Multiple linear regression was performed to determine the influence of age, gender, body weight, delayed graft function (occurring in 24% of patients), acute rejection, pretransplant panel reactive antibody (ranging from 0% to 84%), and the number of human leukocyte antigen mismatches (A, B, and DR loci) on serum creatinine level at last follow-up. For the entire cohort, independent correlates of serum creatinine level at last follow-up were acute rejection (P .0001), pretransplant panel reactive antibody levels (P .05), and body weight (P .004). For the steroid-free group, the independent correlates of serum creatinine at last follow-up were delayed graft function (P .05), panel reactive antibody (P .05), and male gender (P .003). Conclusion: Results of this uncontrolled study suggest that use of SRL and TAC allows the withdrawal of steroid therapy in African American kidney transplant recipients with a low incidence of acute rejection up to 3 years after transplantation. However, steroid withdrawal may be associated with longterm deterioration of renal function, even in the absence of clinically overt acute rejection. In addition to acute rejection, delayed graft function and pretransplant sensitization contribute to declining renal function over time and might be considered relative contraindications to withdrawing steroid therapy from African American kidney transplant recipients in future studies. From the Departments of Medicine and Surgery, University Hospitals of Cleveland, Cleveland, OH. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.029

Is chronic calcineurin inhibitor toxicity responsible for long-term deterioration of renal function in transplant recipients?

Dose reduction or discontinuation of calcineurin inhibitors (CIs) in renal allograft recipients results in a measurable improvement in renal function, as assessed by a decrease in serum creatinine or improvement in glomerular filtration rate. In general, this effect has been presumed to result from a discontinuation of the acute vasoconstrictive action of CIs on the afferent arteriole. Does it reflect the resolution of chronic CI toxicity? Does chronic CI toxicity explain part of the syndrome of chronic allograft nephropathy (CAN)? We have observed evidence of a continued improvement in renal function or a lack of further deterioration after CI dose reduction or discontinuation in patients with CAN. This improvement in renal function remains evident for up to several years after the intervention and is observed even when the period of acute vasoconstriction (6 months after intervention; the period when the greatest rate of change occurs) is taken into account. These findings suggest a detrimental effect of CIs on renal function that may be, at least in part, reversible and independent of vasoconstriction. In this review, we examine the data concerning the relationship between CI and chronic graft dysfunction.