Performance of Different Prediction Equations for Estimating Renal Function in Kidney Transplantation

Numerous formulas have been developed to estimate renal function from biochemical, demographic and anthropometric data. Here we compared renal function derived from 12 published prediction equations with glomerular filtration rate (GFR) measurement by plasma iohexol clearance as reference method in a group of 81 renal transplant recipients enrolled in the Mycophenolate Mofetil Steroid Sparing (MY.S.S.) trial. Iohexol clearances and prediction equations were carried out in all patients at months 6, 9 and 21 after surgery. All equations showed a tendency toward GFR over-estimation: Walser and MDRD equations gave the best performance, however not more than 45% of estimated values were within +/-10% error. These formulas showed also the lowest bias and the highest precision: 0.5 and 9.2 mL/min/1.73 m2 (Walser), 2.7 and 10.4 mL/min/1.73 m2 (MDRD) in predicting GFR. A significantly higher rate of GFR decline ranging from -5.0 mL/min/1.73 m2/year (Walser) to -7.4 mL/min/1.73 m2/year (Davis-Chandler) was estimated by all the equations as compared with iohexol clearance (-3.0 mL/min/1.73 m2/year). The 12 prediction equations do not allow a rigorous assessment of renal function in kidney transplant recipients. In clinical trials of kidney transplantation, graft function should be preferably monitored using a reference method of GFR measurement, such as iohexol plasma clearance.     

Influence of pancreas transplantation alone on native renal function

Pancreas transplantation alone (PTA) has become an accepted treatment of nonuremic diabetic patients, when the risks of secondary complications of diabetes mellitus are greater than those of the surgical procedure and the posttransplant immunosuppression. As a decrease in native renal function is expected, we followed this parameter among patients who underwent PTA. From January 1997 through January 2005, we performed 69 PTA in 66 patients. All patients showed glucose hyperlability with hypoglycemic unawareness, or two or more diabetic complications as well as creatinine clearance (CrCl) > or = 45 mL/min. Immunosuppression was based on tacrolimus, mycophenolate mofetil and prednisone. Twenty-four hour CrCl were performed after all successful PTA. We divided patients in two groups according to the pretransplant CrCl: group 1, CrCl < or = 70 mL/min (n = 20) and group 2, CrCl > 70 mL/min (n = 25). The data were analyzed using Student's t-test (P < or = .05 was considered significant). Twenty-one patients were excluded from the analysis because of death (n = 5) or graft loss (n = 8) during the first year or follow-up shorter than 1 year (n = 8). The mean value of CrCl decreased 28.8% (85.0 +/- 31 versus 60.5 +/- 36 mL/min; P < .001). There was also a 39.3% reduction among group 1 subjects (P = .003), including 10 who displayed CrCl < or = 30 mL/min. There was also a 24.4% reduction among group 2 (P = .008), but no patient developed end-stage renal disease. In conclusion, native renal function decreased significantly after PTA, but was well tolerated among patients with CrCl > 70 mL/min. Patients with CrCl < 70 mL/min show a significant risk of worsened renal function.     

The effect of maintenance immunosuppression medication on the change in kidney allograft function

BACKGROUND: The optimum maintenance immunosuppression regimen for kidney transplant recipients is uncertain. In this study we determined the effect of maintenance immunosuppression medications on the rate of kidney allograft function loss defined by the annualized change in glomerular filtration rate (GFR). METHODS: We studied 40,963 first kidney only transplant recipients between 1987 and 1996 with allograft survival of at least two years in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Patients were classified according to the type of maintenance calcineurin and purine metabolism inhibitor received after transplantation. Multiple linear regression was used to determine the independent effect of maintenance immunosuppression medications on the annualized change in GFR (mL/min/1.73m2/year). RESULTS: Compared to patients who received cyclosporine microemulsion (Neoral), a slower decline in GFR was observed in tacrolimus-treated patients (1.60 mL/min/1.73m2/year, 95% CI 1.22-1.97, P < 0.001) and patients who did not receive calcineurin inhibitors (0.82 mL/min/1.73m2/year, 95% CI 0.08-1.56, P= 0.03). In contrast, compared to compared to patients who received Neoral, a faster decline in GFR was observed in patients who received the original oil-based formulation of cyclosporine (Sandimmune) (-0.16 mL/min/1.73m2/year, 95% CI -0.003 to -0.32, P= 0.04) and patients with unknown calcinuerin inhibitor exposure (-2.11 mL/min/1.73m2/year, 95% CI -2.27 to -1.95, P < 0.001). Compared to patients who received azathioprine, patients who received mycophenolate mofetil (MMF) had a slower decline in GFR (0.61 mL/min/1.73m2/year, 95% CI 0.14-1.08, P= 0.01) and patients with unknown purine metabolism inhibitor exposure had a faster decline in GFR (-0.61 mL/min/1.73m2/year, 95% CI -0.75 to -0.47, P < 0.001.) In a subgroup analysis of patients who received a transplant after 1993, the decline in GFR was slower for tacrolimus compared to neoral treated patients (1.64 mL/min/1.73m2/year, 95% CI 1.15-2.14, P < 0.001) but was not different for MMF compared to azathioprine-treated patients (0.24 mL/min/1.73m2/year, 95% CI -0.38-0.85, P= 0.45). CONCLUSION: Tacrolimus and MMF were the calcineurin inhibitor and purine metabolism inhibitor associated with the most favorable effects on rates of change in allograft function. Because most transplant recipients establish a low baseline level of allograft function, the effect of immunosuppression medication on GFR decline should be considered when selecting a maintenance immunosuppression regimen.     

Kidney function after solitary pancreas transplantation

Preserving kidney function in patients after solitary pancreas transplantation (SPTx) is an important consideration, yet various factors may negatively impact long-term function of the native kidneys or kidney allograft. To determine changes in kidney function over time in a series of patients receiving SPTx, we conducted a retrospective analysis and tracked changes in serum creatinine (SCr) and calculated glomerular filtration rate (GFR) from baseline to 6 months, 1 year, or 3 years after SPTx in a series of pancreas after kidney transplants PAK; (n = 61) and pancreas transplants alone PTA; (n = 27) performed at our institution. The mean follow-up for the PAK and PTA groups was 3.4 and 2.7 years, respectively. In this series, 8% of patients after SPTx developed significant kidney failure, defined by either initiation of dialysis or receiving a kidney transplant (PAK-6, PTA-1). Twenty seven percent of SPTx patients with a baseline GFR < 60 suffered either an elevated SCr > 2.2, dialysis, or kidney transplant, whereas no patients with a baseline GFR > 60 developed significant kidney dysfunction. In the PAK group, the GFR did not show significant deterioration over time. In contrast to relatively stable kidney function in PAK patients, PTA patients experienced overall significantly greater rates of decline over time. GFR in PTA patients decreased from 78 +/- 19 (40 to 114) mL/min/1.73 m2 at baseline to 65 +/- 20 at 1 year (P = .006), while SCr increased from 1.03 +/- 0.25 mg/dL to 1.28 +/- 0.43 over the same time period (P = .012). These data show that kidney function may deteriorate after SPTx and proper patient selection may reduce the frequency of this complication.     

Rate of Renal Graft Function Decline After One Year Is a Strong Predictor of All‐Cause Mortality

The slope of GFR associates with an increased risk for death in patients with native CKD but whether a similar association exists in kidney transplantation is not known. We studied an inception cohort of 488 kidney transplant recipients (mean follow‐up of 12 ± 4 years) for whom GFR was longitudinally measured by inulin clearance (mGFR) at 1 year and then every 5 years. Association of mGFR at 1 year posttransplant and GFR slope after the first year with all‐cause mortality was studied with a Cox regression model and a Fine and Gray competing risk model. While in Crude analysis, the mGFR value at 1 year posttransplant and the rate of mGFR decline were both associated with a higher risk of all‐cause mortality, only the slope of mGFR remained a significant and strong predictor of death in multivariate analysis. Factors independently associated with a more rapid mGFR decline were feminine gender, higher HLA mismatch, retransplantation, longer duration of transplantation, CMV infection during the first year and higher rate of proteinuria. Our data suggest that the rate of renal graft function decline after 1 year is a strong predictor of all‐cause mortality in kidney transplantation.     

Renal function after pediatric intestinal transplant

Data were analyzed from 44 patients who survived more than 2 years after intestinal transplantation performed between 1994 and 2002. Median age was 1.7 years. Tacrolimus level was defined as average tacrolimus level over 6 months. Kidney function was evaluated using a 6-month average serum creatinine. Glomerular filtration rate (GFR) was calculated with the Schwartz formula. The procedures were: isolated intestinal transplantation (n = 11), liver and intestinal transplantation (n = 9), multivisceral transplantation (n = 22), and modified multivisceral transplantation (n = 2). Forty-four patients were followed for a mean of 3.6 years on tacrolimus. Tacrolimus levels ranged between 3.5 and 19.9 ng/mL (median 14.6 ng/mL) at 0 to 6 months and 6.0 to 18.9 ng/mL (median 13.2 ng/mL) at 0 to 12 months. Pretransplant kidney function as mean GFR was 138 +/- 42 mL/min/1.73 m(2) (n = 44), posttransplant kidney function at 18 to 24 month as mean GFR was 102+/-35 mL/min/1.73 m(2) (n = 44), a value that was 81% of the pretransplant GFR (P < .0001). In an analysis of tacrolimus level versus renal function, a value greater than 13.5 ng/mL during the first 12 months was a significant predictor for impaired renal function at 2 years after transplantation (defined as average GFR less than 90 mL/min/1.73 m(2) at 18 to 24 months; P = .001). Only age among age, sex, diagnosis, transplant type, and rejection episodes showed a correlation with renal function. Renal function dropped significantly at 2 years after pediatric intestinal transplantation to 81% of the pretransplantation value. Tacrolimus level for the first 12 months seemed to predict subsequent development of renal impairment at 2 years.     

Independent risk factors and natural history of renal dysfunction in liver transplant recipients

Renal dysfunction is common after liver transplantation. However, there are only limited data on the predictors and natural history of renal dysfunction after liver transplantation. In this study, we determined independent predictors and the natural history of renal dysfunction in 172 consecutive liver transplant recipients. Survival and time to development of permanent renal dysfunction (renal dysfunction defined as a sustained decrease in estimated glomerular filtration rate (GFR) of > 30 mL/min/1.73 m² from baseline for at least 6 months, severe renal failure defined as absolute GFR <30 mL/min/1.73 m² for at least 6 months) were determined using the Kaplan-Meier method. Cox regression analysis was used to test the independent effect of a given set of variables on time to development of such an event. Nine percent of patients required immediate dialysis, 35% developed permanent renal dysfunction, and 7% developed severe renal failure. The rate of decline in renal dysfunction was maximal, 6.5 mL/min/1.73 m² /mo, at 1 month after liver transplantation. Pre-existing diabetes mellitus, major surgical infection, and waiting time on the transplant list were independent risk factors for immediate dialysis. Presence of serum creatinine > 1.2 mg/dL at any time before liver transplantation and a baseline GFR <70 mL/min/1.73 m² were independent predictors of permanent renal dysfunction. Diabetes mellitus, coronary artery disease, and primary graft nonfunction predicted the development of severe renal failure. GFR stabilized around 9 months, and presence of decreased GFR > 30mL/min/1.73 m² from baseline at 9 months predicted development of permanent renal dysfunction. An absolute GFR of <30mL/min/1.73 m² occurring as early as 3 months after liver transplantation predicted severe renal failure. Severe renal failure was associated with a significantly lower survival by Cox regression analysis. We have identified risk factors and the natural history of permanent renal dysfunction and severe liver failure in liver transplant recipients. These observations may be useful in the development of nonnephrotoxic immunosuppressive regimens for high-risk liver transplant recipients. (Liver Transpl 2003;9:741-747.)     

Risk analysis for deterioration of renal function after pancreas alone transplant

The risk of progression to renal replacement after pancreas transplant alone (PTA) is a concern in patients with pre-transplant estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m(2). This is a retrospective, single-center risk analysis of potential factors affecting renal function after PTA. Twenty-four patients, transplanted over a three-yr period, with functioning pancreatic grafts at the study's end point were included. High tacrolimus levels (> 12 mg/dL) at six months post-transplant was the only independent risk factor identifying a substantial decline in native renal function by Cox regression analysis (HR = 14.300, CI = 1.271-160.907, p = 0.031). The presence of severe pre-transplant proteinuria (urine Pr/Cr ≥ 100 mg/mmol) marginally failed to reach significance (p = 0.056). Low eGFR levels alone (≤ 45 and ≤ 40 mL/min/1.73 m(2)) at the time of transplant did not correlate with substantial decline in renal function. Our data suggest that PTA is a justifiable therapy for patients with hypoglycemia unawareness or other life-threatening diabetic complications, even in those with borderline renal function, provided that they do not suffer from severe proteinuria and appropriate monitoring and tailoring of immunosuppression is ensured.     

Nephrological indications in combined liver-kidney transplantation

In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation (LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR < or = 30 to 35 mL/min may be an indication for LKT, but we need more experience.     

Renal function in type 1 diabetics one year after successful pancreas transplantation

Chatzizacharias NA, Vaidya A, Sinha S, Smith R, Jones G, Sharples E, Friend PJ. Renal function in type 1 diabetics one year after successful pancreas transplantation.
Clin Transplant 2011: 25: E509–E515. © 2011 John Wiley & Sons A/S. Abstract: The effect of pancreas transplantation on renal function remains a matter of debate. The purpose of this retrospective, single‐unit study is a preliminary analysis of renal function one yr after pancreas transplant (pancreas alone [PTA] or pancreas after kidney [PAK]). Fifty‐nine patients were included. Serum creatinine and estimated glomerular filtration rate (eGFR) levels were compared three, six, and 12 months post‐transplantation for the whole sample and separately for PTA and PAK and high (>45 mL/min/1.73 m²) and low (≤45 mL/min/1.73 m²) pre‐transplant eGFR subgroups. Overall, eGFR did not change significantly (p = 0.228) at the end of the first year post‐transplant, with patients of low initial eGFR presenting a more prominent trend toward stable or improved levels. In the PAK subgroup, eGFR was significantly improved (p = 0.035). High eGFR subgroup demonstrated no significant deterioration in renal function, while patients with low initial eGFR had significantly higher levels 3 (p = 0.012) and six months (p = 0.009) post‐transplant. Our study shows that renal function did not deteriorate significantly one yr after pancreas transplant (PTA or PAK), even in patients with substantial pre‐existing renal dysfunction. Evaluation at a wider scale and identification of risk factors for potential deterioration are challenges for future research.     

The natural history of renal function following orthotopic heart transplant

BACKGROUND: The outcome of solid organ transplantation has dramatically improved after the introduction of the calcineurin inhibitor cyclosporine. With the increasing longevity of heart transplant recipients, the long-term effects of cyclosporine on renal function have become more evident. The natural history of kidney function following orthotopic heart transplant is not well defined and long-term follow up studies are scant. METHODS: We conducted an observational study on patients who received a heart transplant at Saint Louis University Hospital between January 1, 1983 and December 31, 1988. Patients were followed up for 15 yr or until death whichever occurred first. In order to assess the effect of heart transplantation and cyclosporine exposure on long-term renal function we restricted the statistical analysis to patients who survived the first year post-transplantation. RESULTS: A total of 68 patients received orthotopic heart transplants at Saint Louis University Hospital between 1983 and 1988. Forty-eight (71%) patients survived for more than 1 yr. All patients were treated with cyclosporine based triple immunosuppressive regimen, with gradual cyclosporine dose reduction over time. The mean duration of follow-up was 8 yr. The estimated GFR at 5 and 10 yr post-transplant were significantly lower than estimated GFR at baseline and 1 yr post-transplant. There was no significant difference between estimated GFR at 15 yr and estimated GFR at baseline or 1 yr post-transplant. The cumulative incidence of chronic renal failure (GFR < or = 29 mL/min/1.73 m2) at 5, 10 and 15 yr was 4.2, 10.4 and 12.5%, respectively (p < 0.05). The cumulative incidence of severe chronic renal failure (GFR < or = 15 mL/min/1.73 m2) at 5, 10 and 15 yr was 2.1, 8.3 and 8.3%, respectively. The mortality rate was 8, 37, and 52% at 5, 10, and 15 yr, respectively. The 10 and 15 yr survivors had an estimated GFR at 1 yr post-transplant that was significantly higher than the non-survivors. Age, pre-transplantation estimated GFR, pre-transplantation diabetes and pre-transplantation hypertension are risk factors associated with > or = 10 mL/min/1.73 m2 decrement in estimated GFR. CONCLUSION: Heart transplant survivors beyond the first year post-transplant have a significant decrease in renal function and significant mortality observed over time. Age, pre-transplant GFR, pre-transplant diabetes and pre-transplant hypertension are important risk factors for decrement in renal function.     

Long-term renal outcome after lung transplantation is predicted by the 1-month postoperative renal function loss

BACKGROUND: Progressive renal function loss is common after lung transplantation. To facilitate the design of renoprotective strategies, identification of early predictors for long-term renal function loss would be useful. METHODS: We prospectively analyzed renal function [glomerular filtration rate (GFR); 125I-iothalamate clearance] in a closely monitored cohort (minimum 24-month follow-up) of 57 patients who received lung transplants between November 1990 and September 1996 in our center. The analyzed end points were the slope of the GFR from 6 months posttransplant onward and the GFR at 24 months after transplantation. RESULTS: Before transplantation, the GFR was 100 ml/min (median, range 59-163). It decreased to 67 ml/min (29-123) at 6 months, 53 ml/min (17-116) at 24 months, and 51 ml/min (20-87) at 36 months after transplantation. The magnitude of the loss of GFR 1 month post-transplantation was the only factor significantly correlated with absolute GFR at 24 months after transplantation. Pulmonary diagnosis was significantly associated with long-term rate of renal function loss. Median loss of GFR was greatest in patients with cystic fibrosis (-10 ml/min/year, range -14 to -6 ml/min/year), preserved in pulmonary hypertension (-1 ml/min/year, range -6 to +7 ml/min/year), and in between in emphysema (-6 ml/min/year, range -27 to +12 ml/min/year). No other factors could be identified. CONCLUSIONS: In lung transplant recipients, the 1-month postoperative loss of GFR is an early marker for long-term renal prognosis. Pulmonary diagnosis appears to be a relevant predictor as well. These factors may guide further research and the development of preventive strategies.     

MDRD Equations for Estimation of GFR in Renal Transplant Recipients

After renal transplantation monitoring and detection of slight-to-moderate changes in GFR is a prerequisite for an optimal patient management. Recently, several equations to estimate GFR were developed and verified in the MDRD study cohort. However, little is known about the application of the MDRD formulas in the setting of renal transplantation. We prospectively conducted a study of the GFR estimates of the Cockcroft and Gault (C&G), MDRD6-, MDRD7 and the abbreviated MDRD (aMDRD) with the true GFR as measured by (99m)Tc-DTPA clearance in 95 consecutive patients 6.5, 5.3-7.7 years (mean, 95% CI) after renal transplantation. On average the DTPA clearance was 37.4, 34.4-40.4 mL/min/1.73 m(2), which differed significantly from estimates of GFR by C&G (52.6, 48.3-56.9 mL/min/1.73 m(2)), MDRD7 (44.8, 40.7-49.0 mL/min/1.73 m(2)), MDRD6 (43.8, 39.9-47.7 mL/min/1.73 m(2)) and aMDRD (46.6, 42.4-50.9 mL/min/1.73 m(2)). Bias was lowest for MDRD6 (6.4 mL/min/1.73 m(2)) and highest for C&G (15.2 mL/min/1.73 m(2)). Precision was similar for MDRD7 and aMDRD (10.6 and 11.1 mL/min/1.73 m(2)) but significantly better for MDRD6 (8.6 mL/min/1.73 m(2); p < 0.035). Accuracy within 50% of real GFR was 55.8% for C&G, 83.2% for aMDRD, 87.4% for MDRD7 and 90.5% for MDRD6. MDRD equations perform significantly better than the commonly used C&G formula. Moreover, the MDRD6 equation provides the best diagnostic performance, and should therefore be preferred in renal transplant recipients.     

Why do preemptive kidney transplant recipients have an allograft survival advantage?

BACKGROUND: Preemptive kidney transplantation is associated with an allograft survival advantage and is promoted in part because of this association. The basis for the allograft survival advantage in preemptive recipients is unclear. Possibilities include a lead time bias due to the earlier transplantation of patients with preserved native kidney function, less rapid loss of kidney function after transplantation, or the longer patient survival of preemptive recipients. METHODS: We compared the glomerular filtration rate (GFR) six months after transplantation and the subsequent rate of loss of kidney function as defined by the annualized change in GFR (mL/min/1.73 m2/year) in 5,966 preemptive and 34,997 non-preemptive recipients. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Multiple regression was used to determine the independent effect of preemptive transplantation upon the annualized change in GFR. RESULTS: The mean GFR six months after transplantation was similar among preemptive (49.5+/-15.7 mL/min/1.73 m2) and non-preemptive (49.2+/-14.7 mL/min/1.73 m2) recipients (P=0.37). In multivariate analysis, preemptive recipients had a slower decline in GFR (0.28 mL/min/year/1.73 m2; 95% confidence interval 0.11, 0.46; P=0.002). However, this difference was of modest clinical significance and would not explain the allograft survival advantage of preemptive transplantation. CONCLUSIONS: Neither the preservation of native kidney function nor differences in the rate of loss of kidney function explain the superior allograft survival of preemptive recipients. By exclusion, the allograft survival advantage associated with preemptive transplantation may be due to the longer survival of preemptive recipients.     

Renal impairment and diabetes mellitus after liver transplant

INTRODUCTION: One of the major concerns in liver transplant patients who survive past 1 year posttransplant is the development of chronic diseases. AIM: We studied two important clinical conditions that can have a chronic course-renal impairment and diabetes mellitus-among long-term liver transplant survivors. METHODS: All adult patients transplanted and followed for at least 1 year were evaluated for clinical status, blood tests, and imaging studies. The occurrence and development of renal impairment, defined as a serum creatinine above 125 micromol/L or creatinine clearance less than 75 mL/min, or diabetes mellitus were evaluated for contributing factors. RESULTS: The 35 evaluated patients of mean age at transplant of 50 years had a mean follow-up duration of 45 months. The incidence of posttransplant renal impairment was 22.8% at 1 year and 47.6% at 3 years. This disorder was associated with pretransplant renal impairment and with a diagnosis of diabetes. Posttransplant diabetes mellitus was observed in 48.6% with 41.1% resolving over time. CONCLUSION: Posttransplant renal impairment appears to be a potential long-term problem. Although this relates to pretransplant conditions, longer follow-up is required to examine whether posttransplant factors contribute to its progression.     

The Clinical Impact of an Early Decline in Kidney Function in Patients Following Heart Transplantation

Renal dysfunction is a well-known complication following heart transplantation. We examined an early decline in kidney function as a predictor of progression to end-stage renal disease and mortality in heart transplant recipients. We performed a retrospective cohort study of 233 patients who received a heart transplant between July 1985 and July 2004, and who survived >1 month. The decline in estimated creatinine clearance (CrCl) was used to predict the outcomes of need for chronic dialysis or mortality >1-year posttransplant. The earliest time to chronic dialysis was 484 days. A 30% decline in CrCl between 1 month and 12 months predicted the need for chronic dialysis (p = 0.01), all-cause mortality (p < 0.0001) and time to first CrCl ≤30 mL/min at >1-year posttransplant (p = 0.02). A 30% decline in CrCl between 1 month and 3 months also independently predicted the need for chronic dialysis (p = 0.04) and time to first CrCl ≤ 30 mL/min at >1-year posttransplant (p = 0.01). In conclusion, an early drop in CrCl within the first year is a strong predictor of chronic dialysis and death >1-year postheart transplantation. Future studies should focus on kidney function preservation in those identified at high risk for progression to end-stage kidney disease and mortality.     

Modifiable patient factors are associated with the late decline in renal function following liver transplantation

Strategies to delay or avoid the long-term decline in renal function and progression to chronic kidney disease (CKD) in liver transplant recipients remain unclear. Our aim was to examine the change in estimated GFR (eGFR) from six months after liver transplantation, and to identify modifiable factors associated with a faster rate of decline. This was a single-center retrospective study of 97 patients who underwent elective liver transplantation and survived ≥ 5 yr. eGFR was estimated using the MDRD6-variable equation, and the annualized change in eGFR was determined using simple linear regression. The baseline eGFR was 75 mL/min/1.73 m(2) . Thereafter, eGFR declined at a mean rate of 1.08 mL/min/1.73 m(2) per year. 49% had a decline in renal function greater than the rate expected with aging. Decline in eGFR was an independent predictor of CKD by five yr post-transplant (p = 0.001). Multivariate modeling found a higher baseline eGFR (p < 0.001), female gender (p = 0.006), hypertension (p = 0.019), and dyslipidemia (p = 0.034) to be associated with a faster rate of decline in renal function. In conclusion, liver transplant recipients have a clinically relevant decline in eGFR from six months post-transplant. Prospective studies are required to examine the effects of aggressive blood pressure and lipid control on the development of CKD in this setting.     

The plasma creatinine concentration is not an accurate reflection of the glomerular filtration rate in stable renal transplant patients receiving cyclosporine

We studied 31 stable renal cadaver kidney transplant patients receiving cyclosporine (CyA) and prednisone for immunosuppression to determine what reduction in true glomerular filtration rate (GFR) was reflected by their mild elevation in plasma creatinine concentration (1.8 +/- 0.11 mg/dL). We measured both the creatinine clearance (60 +/- 4.32 mL/min/1.73 m2) and the true GFR using Technetium 99m-DTPA (44 +/- 2.72 mL/min/1.73 m2). The creatinine clearance overestimated true GRF by a mean of 38%, indicating that this percentage of creatinine reached the urine by tubular secretion rather than glomerular filtration. A similar degree of overestimation was found in a separate group of 14 patients receiving imuran for immunosuppression. In 23 patients receiving CyA in whom the serum creatinine concentration was less than 2.0 mg/dL, the mean DTPA clearance was 49.5 +/- 2.83 mL/min/1.73 m2. In stable renal transplant patients receiving CyA, a serum creatinine concentration at, or close to, the upper limit of the normal range may reflect markedly impaired renal function.     

Hyperuricaemia in cyclosporin-treated patients: a GFR-related effect

BACKGROUND: Hyperuricaemia is a well known side-effect of cyclosporin A(CsA) treatment. The pathogenic mechanisms, however, remaincontroversial. There is no convincing evidence that hyperuricaemiais due to CsA-induced, impaired tubular handling of uric acid.The impact of diminished GFR in this particular context hasnever been investigated. METHODS: We prospectively studied plasma uric acid, inulin clearances,and fractional clearances of uric acid in two groups of CsA-treatedpatients (bone-marrow transplant patients, n=50; renal transplantpatients, n=32), and one healthy control group without CsA (livingrelated kidney donors, n=28). Bone-marrow transplant patientswere examined before transplantation and 6, 12, 18, 24 monthsafter transplantation, renal transplant patients 1 year aftertransplantation, and living related kidney donors before and1 year after unilateral nephrectomy. RESULTS: After 1 year of CsA treatment, hyperuricaemia was found in 36%of bone-marrow transplant patients and in 53% of renal transplantpatients. Thirty per cent of living related kidney donors wereborderline hyperuricaemic 1 year after unilateral nephrectomy.The fractional clearance of uric acid, measured serially inbone-marrow transplant patients did not change significantlyover time; it was, however, slightly higher during CsA treatmentthan after CsA withdrawal. Moreover, the bone-marrow transplantpatients' fractional clearance of uric acid was not statisticallydifferent from the renal transplant patients' and the livingrelated kidney donors' (values 1 year after transplantation/unilateralnephrectomy: bone-marrow transplant patients, 15.3±2.3%;renal transplant patients, 11.9±0.9%; living relatedkidney donors, 11.1±0.8%). The GFR at 1 year, measuredby inulin clearance, was identical in the CsA-treated groupsand slightly higher in the living related kidney donors (bone-marrowtransplant patients, 51±6 ml/min per 1.73 m² renal transplantpatients, 49±3 ml/min per 1.73 m² living related kidneydonors, 61±2 ml/min per 1.73 min²). CONCLUSIONS: There is no evidence for impaired tubular handling of uric acid,induced by a CsA-specific tubulotoxic effect. Hyperuricaemiain CsA-treated transplant patients can therefore be attributedto the cyclosporin associated decrease of GFR.     

Renal dysfunction following adult intestinal transplant under tacrolimus-based immunosuppression

We analyzed data from the records of 24 adult patients who survived more than 2 years after intestinal transplantation performed between 1995 and 2002 under tacrolimus-based immunosuppression. Ages ranged from 19.3 to 59.2 years old (median 32.1 years). Tacrolimus cumulative level was defined as a sum of weekly average tacrolimus level over time. Kidney function was evaluated by the 6-month average serum creatinine level. Estimated creatinine clearance was calculated with the Cockcroft-Gault formula. Student's t test was used for analysis. Primary diseases were mesenteric thrombosis (n = 7), trauma (n = 4), Crohn's (n = 3), Gardner's (n = 5), and others (n = 7). Procedures were isolated intestinal transplant (n = 10), liver and intestine (n = 1), multivisceral transplant (n = 9), or modified multivisceral transplant (n = 4). Cumulative tacrolimus levels ranged between 1161 and 8623 ng*day/mL (median 4132 ng*day/mL) at 0 to 12 months. Pretransplant kidney function as mean creatinine clearance was 114 mL/min per 1.73 m(2) (n = 24). Creatinine clearance decreased to a mean of 49.6 mL/min per 1.73 m(2) (43.5% of pretransplant) at 2 years (P < .0001). The average creatinine clearance at 18 to 24 months in each patient with a cumulative tacrolimus level <4500 ng*day/mL was 63% +/- 25% of preoperative creatinine clearance. In patients with a cumulative tacrolimus level >4500 ng*day/mL, it was 34% +/- 17%. Cumulative tacrolimus level >4500 ng ng*day/mL was significantly associated with a decreased creatinine clearance at 2 years (P = .006). Renal function decreased significantly after intestinal transplantation in adults. Cumulative tacrolimus level in the first year affected renal function at 2 years.