Decline in kidney function before and after nephrology referral and the effect on survival in moderate to advanced chronic kidney disease.

BACKGROUND: The burden of chronic kidney disease (CKD) is high, but its natural history and the benefit of routine nephrology care is unclear. This study investigated the decline in kidney function prior to and following nephrology referral and its association with mortality. METHODS: This study provides a retrospective review of the individual rates of glomerular filtration rate (GFR) decline (millilitre per minute per 1.73 m(2)/year) for the 5 years before and after referral in 726 new referrals with stages 3-5 CKD to one renal unit between 1997 and 2003. Blood pressures are averages at referral, 1 and 3 years post referral. Logistic regression and Cox's models tested factors predicting post-referral GFR decline and the impact on mortality. RESULTS: Mean (SD) age was 72 (14), and 389 (54%) patients had stages 4-5 CKD. GFR decline slowed significantly from -5.4 ml/min/1.73 m(2)/year (-13. to -2) before to -0.35 ml/min/1.73 m(2)/year (-3 to +3) after referral (P < 0.001). Blood pressure also reduced significantly (155/84 to 149/80, P < 0.05) with most changes occurring within 1 year of referral. Factors predicting a non-progressive post-referral decline included a lower systolic blood pressure at referral and 1 year after referral, a CKD diagnosis other than diabetic nephropathy, less baseline proteinuria and a non-progressive pre-referral GFR decline. A non-progressive post-referral GFR decline was independently associated with significantly better survival (hazard ratio 0.55, 95% CI 0.40-0.75, P 相似文献   

Earlier Is Not Necessarily Better in Preemptive Kidney Transplantation

While preemptive (before chronic dialysis) transplantation is associated with improved graft survival, it is unclear whether higher versus lower pretransplant kidney function is associated with even better graft survival after preemptive transplantation. We examined 671 first, preemptive, kidney‐only transplantations at Hennepin County Medical Center and the University of Minnesota Medical Center 1984–2006. We estimated pretransplant glomerular filtration rate (eGFR, mL/min/1.73 m²) using the Modification of Diet in Renal Disease (MDRD) equation with Group 1: <10.0 (7.3 ± 1.7, N = 324), Group 2: 10.0–14.9 (12.0 ± 1.4, N = 217) and Group 3: ≥15.0 (21.1 ± 10.0, N = 130). The mean difference in eGFR for Group 1 versus 3 was 13.8 pretransplant, 16.3 on day 1 and 13.9 on day 2 posttransplant. By week 1 and year 1 posttransplant, the differences between Groups 1 and 3 reduced to 6.3 and 4.5 mL/min/1.73 m², respectively. The adjusted relative risk (RR; Cox analysis) for graft failure was not significantly lower with higher pretransplant eGFR (reference eGFR <10.0); RR = 0.99 (95% confidence interval = 0.68–1.44, p = 0.9432) for eGFR 10.0–14.9; RR = 1.35 (0.89–2.05, p = 0.1588) for eGFR ≥15. Thus, early preemptive transplantation with higher eGFR does not necessarily improve graft survival after kidney transplantation, compared to preemptive transplantation with lower pretransplant eGFR.     

Anemia: A Continuing Problem Following Kidney Transplantation

Cardiovascular disease is a leading cause of death among kidney transplant recipients. Anemia, a risk factor for cardiovascular complications among patients with chronic kidney disease, has not been well characterized in kidney transplant recipients. We performed a retrospective cohort study of the prevalence of and factors associated with anemia among 240 patients who underwent kidney transplantation at our institution. The mean hematocrit (Hct) rose from 33% at 1 month after transplantation to 40% at 12 months after transplantation. The proportion of patients with Hct < 36% was 76% at transplantation and 21% and 36%, 1 year and 4 years after transplantation, respectively. Six months after transplantation, women had higher likelihood (OR = 3.61) of Hct < 36%, while higher Hct at 3 months (OR = 0.67 for 1% higher Hct) and diabetes (OR = 0.14) were associated with a lower likelihood of Hct < 36%. Similar associations were seen 12 months after transplantation. Even among patients with Hct < 30%, only 36% had iron studies, 46% received iron supplementation and 40% received recombinant human erythropoietin. Awareness of factors associated with a lower Hct may prompt better anemia screening and management, potentially improving cardiovascular outcomes among kidney transplant recipients.     

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.     

Hyperlipidemia Is Associated With Accelerated Chronic Kidney Disease Progression After Lung Transplantation

Hyperlipidemia is associated with faster progression of chronic kidney disease (CKD) in the general public. We sought to investigate this association after lung transplantation. Data was retrospectively collected on 230 lung recipients transplanted between January 1997 and December 2003. Estimated glomerular filtration rates (eGFR) and lipid levels were recorded at regular intervals posttransplant. Independent associations between lipid levels early posttransplant and pertinent renal endpoints were investigated. Baseline LDL was 110 ± 35 mg/dL and remained unchanged at 6 months. A faster decline in eGFR was seen in those with 6 month LDLs > versus < the mean level of 110 mg/dL (p = 0.05). By 6 months posttransplant eGFRs were lower in the 6 month LDL > versus < 110 mg/dL group (53 ± 23 vs. 62 ± 29 mL/min/1.73 m², p = 0.01), a difference that persisted at 60 months (39 ± 24 vs. 73 ± 57 mL/min/1.73 m², p = 0.05). On univariate analysis, a 6 month LDL in the highest quartile, i.e. >140 mg/dL, predicted faster progression to CKD, defined as declining to an eGFR < 30 mL/min/1.73 m² (HR 1.5, p = 0.01). This finding persisted in the multivariate Cox-proportional model (HR 1.4, p = 0.02). Hyperlipidemia predicts faster decline in renal function after lung transplant. Prospective trials are needed to confirm this finding.     

Preservation of residual renal function and factors affecting its decline in patients on peritoneal dialysis

SUMMARY:     The decline of residual renal function (RRF) in peritoneal dialysis (PD) patients was analysed and assessed, and risk factors affecting its decline were identified. Residual glomerular filtration rate (GFR) was calculated from averaging the urea and creatinine clearance by 24-h urine collection, and peritoneal solute removal was evaluated by creatinine clearance calculated from 24-h effluent collection. Both GFR and peritoneal solute removal were chronologically examined in 34 PD patients from the time of initiation, and risk factors associated with rapid GFR decline were investigated. The RRF contributed to 43.1 ± 17.6% of total (peritoneal and renal) weekly creatinine clearance at 1 month after initiation of PD. Residual GFR, however, declined continuously with time (−0.19 ± 0.14 mL/min per month), and the reduction rate was high with a higher GFR, higher normalized dietary protein intake, higher urine volume and higher urine protein excretion at the initiation of PD. Other factors related to the rapid decline of GFR were: being older than 60 years of age, automated peritoneal dialysis (APD) rather than continuous ambulatory peritoneal dialysis, mean blood pressure higher than 110 mmHg, and serum human atrial natriuretic peptide level higher being than 60 pg/dL. These data suggest that while RRF plays an important role in the removal of uraemic solute in PD patients, they show a significant decrease over 2 years. The factors related to the rapid decline of GFR corresponded to older age, modality of PD (APD), higher GFR and higher amount of urine protein at initiation, higher dietary protein intake, and inadequate control of hypertension and body fluid volume.     

Functional renal reserve capacity in different stages of chronic kidney disease

Aim: There is conflict in published reports on the extent of availability of the functional renal reserve (RR) in healthy adults and in various stages of chronic kidney disease (CKD). The aim of the present study was to determine the RR in various stages of CKD. Methods: Baseline glomerular filtration rate (GFR) and ‘stimulated GFR’ following amino acid infusion were measured in 25 volunteers and 100 patients at various stages of CKD by measuring plasma clearance of Tc99m diethyl triamine pentaacetic acid. Any obtained difference between stimulated and basal GFR was considered as RR and expressed as percentage. Results The mean renal reserve was 23.4% in the healthy control group, 19.08% in CKD stage 1, 15.4% in CKD stage 2, 8.9% in CKD stage 3 and 6.7% in CKD stage 4, respectively. Conclusion: Renal reserve falls relentlessly with progression of CKD from 23.4% in normal to 6.7% in stage 4 CKD. However, RR may also get completely exhausted even with a normal or with a minimal decline basal GFR. Kidneys may retain some RR even up to the GFR level of 15 mL/min.     

Estimation of the glomerular filtration rate in children and young adults by means of the CKD-EPI equation with age-adjusted creatinine values

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Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all‐cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49±18 mL/min/1.73 m². In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m² higher eGFR at levels below 45 mL/min/1.73 m² was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m². In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.     

Framing Disparities Along the Continuum of Care from Chronic Kidney Disease to Transplantation: Barriers and Interventions

Research in renal transplantation continues to document scores of disparities affecting vulnerable populations at various stages along the transplantation process. Given that both biological and environmental determinants contribute significantly to variation, identifying factors underlying an unfairly biased distribution of the disease burden is crucial. Confounded definitions and gaps in understanding causal pathways impede effectiveness of interventions aimed at alleviating disparities. This article offers an operational definition of disparities in the context of a framework aimed at facilitating interventional research. Utilizing an original framework describing the entire continuum of the transplant process from diagnosis of chronic kidney disease through successful transplant, this article explores the case of racial disparities, illustrating key factors predicting and perpetuating disparities. Though gaps in current research leave us unable to identify which stages of the transplant pathway adversely affect most people, by identifying key risk factors across the continuum of care, this article highlights areas suited for targeted interventions and presents recommendations for improvement and future research.     

Outcomes and Native Renal Recovery Following Simultaneous Liver–Kidney Transplantation

With the increase in patients having impaired renal function at liver transplant due to MELD, accurate predictors of posttransplant native renal recovery are needed to select candidates for simultaneous liver–kidney transplantation (SLK). Current UNOS guidelines rely on specific clinical criteria for SLK allocation. To examine these guidelines and other variables predicting nonrecovery, we analyzed 155 SLK recipients, focusing on a subset (n = 78) that had post‐SLK native GFR (nGFR) determined by radionuclide renal scans. The 77 patients not having renal scans received a higher number of extended criteria donor organs and had worse posttransplant survival. Of the 78 renal scan patients, 31 met and 47 did not meet pre‐SLK UNOS criteria. The UNOS criteria were more predictive than our institutional criteria for all nGFR recovery thresholds (20–40 mL/min), although at the most conservative cut‐off (nGFR ≤ 20) it had low sensitivity (55.3%), specificity (75%), PPV (67.6%) and NPV (63.8%) for predicting post‐SLK nonrecovery. On multivariate analysis, the only predictor of native renal nonrecovery (nGFR ≤ 20) was abnormal pre‐SLK renal imaging (OR 3.85, CI 1.22–12.5). Our data support the need to refine SLK selection utilizing more definitive biomarkers and predictors of native renal recovery than current clinical criteria.     

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.     

National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without Race

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Estimated Glomerular Filtration Rate from Serum Cystatin C: Significant Differences among Several Equations Results

Objectives: Several equations for the estimation of glomerular filtration rate (GFR) from serum cystatin C have been reported. We compared the results obtained using these equations to test the homogeneity of their results as well as their usefulness in clinical practice. Design and methods: Seven hundred and twenty-seven outpatients were studied. Of these, 439 were male and 288 were female, and their mean age was 60.8 ± 24.1 years. GFR was estimated from serum creatinine using the abbreviated Modification of Diet in Renal Disease (MDRD-4) equation. GFR was estimated from serum cystatin C levels using five different equations. Results: The simplest (100/cystatin C) formula rendered the highest estimated GFR and the Hoek’s equation rendered the lowest GFR, even significantly lower than the MDRD-4 equation (p < 0.001, Student’s t-test). From the simplest formula to the Hoek equation the mean difference calculated was 25.1 ± 8.7 mL/min (p < 0.001, Student’s t-test). No differences by gender were found among the results of different equations. All cystatin C-derived equations reduced the number of patients diagnosed of chronic renal failure when compared with MDRD-4 formula. No patient with normal renal function was shifted to the renal disease group. Conclusions: A higher value could be expected when GFR is estimated from cystatin C. Nevertheless, vast differences were found in the results when tested using several equations. Physicians should be aware of this problem to avoid a wrong clinical diagnosis of renal function.     

Can a Transplanted Living Donor Kidney Function Equivalently to its Native Partner?

Early renal functional adaptation was examined in 81 haploidentical donor and recipient pairs, as well as long-term stability of glomerular filtration rate (GFR) in 78 recipients. GFR was determined pre- and 1 month postnephrectomy in donors and 1 month post-transplant and yearly thereafter in recipients. Compensatory increase in filtration (CIF) of transplanted and native kidneys was calculated using donor pretransplant GFR: [CIF= (GFR at 1 month/donor prenephrectomy GFR) x 100]. Annual rates of change in GFR were estimated using within-patient linear regression analysis (slopes). Recipients without rejection (n = 62) and their donors had similar early GFR and CIF. Those with acute rejection (n = 19) had significantly lower GFR and CIF than their donors (61 +/- 16 mL/min/1.73 m2 and 57 +/- 14% vs. 75 +/- 11 and 69 +/- 9; p = 0.01 and p < 0.001). Recipients without cyclosporine (n = 52) had 1 month GFR and CIF of 70 +/- 14 and 67 +/- 14 vs. 72 +/- 11 and 69 +/- 11 for their donors. Those with cyclosporine (n = 29) had 1 month GFR and CIF of 64 +/- 14 and 62 +/- 16 vs. 69 +/- 12 and 67 +/- 11 for their donors (p = 0.15 and 0.16). Comparison of median (25th, 75th) rates of change of GFR with and without acute rejection or cyclosporine did not demonstrate significant effects of either on stability of allograft function, although there was a trend towards greater loss of GFR in cyclosporine-treated patients [-1.1 (-2.5, 0.8) vs. 0.0 (-1.8, 1.2) mL/min/1.73 m2/year, p = 0.47]. We conclude that, in the absence of rejection, the transplanted kidney maintains the same capacity for functional adaptation as its native partner. Therapy with cyclosporine does not significantly inhibit early physiological adaptation of renal transplants.     

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5–15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.