The inevitability of renal function loss in patients with hypercreatinemia.

UNLABELLED: Although it is anticipated that most patients with renal insufficiency will progress towards end-stage renal disease (ESRD) there have been few population-based studies to validate this assumption. We examined serial creatinines from 3,874 anonymous patients at an urban VA medical center who had a baseline creatinine of 1.4 mg/dl or greater to estimate the frequency of deterioration in renal function (DRF). DRF was defined as the first Cr (1stCr) value being lower than the last Cr (LCr) for each patient. The median follow-up was 48.3 +/- 0.5 months with 18 +/- 0.5 creatinine values per patient. The median 1stCr was 1.6 +/- 0.1 mg/dl with 32.2% of the patients having a 1stCr greater than or equal to 1.7 mg/dl. In the study group, 1,723 (44.4%) had DRF including 1,089 (41.4%) of those patients with a 1stCr of 1.4-1.7 mg/dl. However, 45 (36.6%) of those with a 1stCr value 3.0-5.0 mg/dl did not have DRF, the percent with stable creatinine in this group did not vary with length of follow-up. Over the study period, 299 (7.7%) of all the patients had a creatinine rise to 7.0 mg/dl, with 104 (4%) of those with a 1stCr of 1.4-1.7 mg/dl reaching this endpoint. CONCLUSION: A majority, but not all, patients with renal insufficiency lose renal function over time and those with even mild hypercreatinemia are at risk for deterioration in renal function. Hypercreatinemia, however, does not accurately discriminate between those renal insufficiency patients who are stable versus those at high risk for ESRD.

Long-term impact of discontinued or reduced calcineurin inhibitor in patients with chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy is the major cause of progressive renal failure in renal transplant recipients. It has no definitive treatment. METHODS: One hundred eighteen renal transplant recipients with declining kidney function and biopsy-proven chronic allograft nephropathy had their cyclosporine or tacrolimus dose reduced or discontinued with either the addition or continuation of mycophenolate mofetil and low-dose steroids at a mean of 853.3 days post-transplantation. Their renal function was modeled before and after this intervention by two methods: A least-square regression was used to assess the decay of renal function after the intervention and to compare that with the slope pre-intervention, whereas a hinge regression line method was used to assess the correlation of the intervention with the inflection point and the impact of the intervention on the decay of renal function. Mean follow-up was 651.0 days after the intervention. Serum creatinine at the time of intervention was 2.8 +/- 0.9 mg/dL in the reduced dose cyclosporine (N = 67) and reduced dose tacrolimus (N = 33) groups, and was 2.7 +/- 0.7 mg/dL in the group with discontinued calcineurin inhibitor (N = 18). RESULTS: Using the least-square method, 91.7% of the no calcineurin inhibitor group, 51.6% of the reduced dose cyclosporine group, and 59.3% of the reduced dose tacrolimus group had improved or lack of deterioration in slope after the intervention. Using the hinge regression line method, there was a statistically significant correlation of the inflection point with the intervention (P = 0.001). Moreover, there was a similar relationship with stabilized or improved graft function observed with the hinge regression line method and the least-square method, as 72.2% of the calcineurin inhibitor withdrawal group, 54.4% of reduced-dose cyclosporine group, and 40% of the reduced-dose tacrolimus group had improved the slope of decay of renal function or lack of deterioration after the inflection point. The difference between the calcineurin inhibitor withdrawal group and the reduced-dose cyclosporine/tacrolimus groups on the decay in renal function was significant (P = 0.038) with the least-square method and nearly significant (P = 0.056) using the hinge regression line method. CONCLUSION: This intervention was safe, well tolerated, and associated with a minimal risk of acute rejection. We conclude that the reduction and possible withdrawal of calcineurin inhibitors may be necessary to slow the rate of loss of renal function in patients with chronic allograft nephropathy and deteriorating renal function.

Significance of serum creatinine values in new end-stage renal disease patients.

The appropriate use of serum creatinine level as a surrogate for time in the course of renal failure when dialysis commences requires it to be a significant predictor of mortality in incident patients with end-stage renal disease (ESRD). This study evaluated factors that account for variations in creatinine level before the initiation of dialysis and whether incident creatinine level after controlling for these factors was a risk factor for mortality. This is a retrospective cohort study of patients from Maryland and Virginia who initiated dialysis between April 1, 1995, and December 31, 1996, with data ascertained from the Health Care Financing Administration Form 2728. Multivariate models were used to evaluate both the factors that predict incident serum creatinine level and the association between creatinine level and mortality. There were 5, 388 patients followed up for an average of 23.6 +/- 0.2 months. Mean creatinine level was 9.2 +/- 0.1 mg/dL, with case-mix factors most predictive of serum creatinine level and accounting for 9% of its variance. Hematocrit and blood urea nitrogen levels as additional surrogates for progression of renal disease accounted for 7.4% of the variance, whereas the nutritional parameters, body mass index, and albumin level only explained an additional 1% of the total variance in creatinine level. Creatinine level was inversely correlated with mortality risk, and this relationship was sustained both with transformation into an estimated glomerular filtration rate and multivariate adjustment for confounders (relative risk = 0. 96; P < 0.0001). Creatinine values from an incident ESRD population have a weak relationship with the timing of dialysis initiation but represent a strong measure of health status.