Tubular secretion of creatinine and kidney function: an observational study.

BackgroundPrior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR). A recent cross-sectional study suggested that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio is larger when GFR is lower among patients with chronic kidney disease (CKD); but there have been no validation of this in other cohorts.MethodsTo fill these gaps in knowledge regarding the relation between CrCl and GFR, we conducted cross-sectional and longitudinal analysis of the Modification of Diet in Renal Disease study (MDRD) and African American Study of Kidney Disease and Hypertension (AASK); and cross-sectional analysis of a clinical dataset from the Mayo Clinic of four different patient populations (CKD patients, kidney transplant recipients, post kidney donation subgroup and potential kidney donors). In the cross-sectional analyses (MDRD, AASK and Mayo Clinic cohort), we examined the relation between the CrCl/iothalamate GFR (iGFR) ratio at different categories of iGFR or different levels of CrCl. In the MDRD and AASK longitudinal analyses, we studied how the CrCl/iGFR ratio changed with those who had improvement in iGFR (CrCl) over time versus those who had worsening of iGFR (CrCl) over time.ResultsObserved CrCl/iGFR ratios were generally on the lower end of the range reported in the literature for CKD (median 1.24 in MDRD, 1.13 in AASK and 1.25 in Mayo Clinic cohort). Among CKD patients in whom CrCl and iGFR were measured using different timed urine collections, CrCl/iGFR ratio were higher with lower iGFR categories but lower with lower CrCl categories. However, among CKD patients in whom CrCl and iGFR were measured using the same timed urine collections (which reduces dis-concordant measurement error), CrCl/iGFR ratio were higher with both lower iGFR categories and lower CrCl categories.ConclusionsThese data refute the recent suggestion that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio increases as GFR decreases in CKD patients. They also highlight the lack of certainty in our knowledge with regard to how much CrCl actually overestimates GFR

The association between benign prostatic hyperplasia and chronic kidney disease in community-dwelling men

The association between benign prostatic hyperplasia and chronic kidney disease in community-dwelling men.BackgroundBenign prostatic hyperplasia (BPH) and chronic kidney disease are important public health problems in older men. Previous referral-based studies disagree on whether BPH is associated with chronic kidney disease. The objective of this study was to determine the community-based association between clinical measures of BPH and chronic kidney disease.MethodsA community-based sample of 2115 white men (ages 40–79 years) was randomly selected from the Olmsted County, Minnesota population (55% participation rate) in 1990. A random subsample (N = 476) had a detailed clinical evaluation. This evaluation included a questionnaire with similar queries to the International Prostate Symptom Score (IPSS), peak urinary flow rates (uroflowmeter), postvoid residual urine volume (ultrasound), prostate volume (ultrasound), serum prostate specific antigen (PSA), and serum creatinine.ResultsAfter adjustment for age, hypertension, diabetes, leukocyte esterase positive (possible urinary tract infection), and smoking, chronic kidney disease [serum creatinine ≥133 μmol/L (1.5 mg/dL)] was associated with diminished peak urinary flow rate (<15 mL/sec) by an odds ratio (OR) = 2.96 (95% CI 1.30–7.01), moderate-severe lower urinary tract symptoms (IPSS >7) by an OR = 2.91 (95% CI 1.32–6.62), and chronic urinary retention (postvoid residual >100 mL) by an OR = 2.28 (95% CI 0.66–6.68). There was no association with a prostate volume >30 mL by an OR = 0.56 (95% CI 0.22–1.37) or PSA >1.4 ng/mL by an OR = 1.17 (95% CI 0.47–2.81).ConclusionThere was a cross-sectional association between signs and symptoms of bladder outlet obstruction and chronic kidney disease in community-dwelling men. Prostatic enlargement was not associated with chronic kidney disease

Living Kidney Donation:A Narrative Review of Mid- and Long-term Psychosocial Outcomes

Living kidney donors make a significant contribution to alleviating the organ shortage. The aim of this article is to provide an overview of mid- and long-term (≥12 mo) living donor psychosocial outcomes and highlight areas that have been understudied and should be immediately addressed in both research and clinical practice. We conducted a narrative review by searching 3 databases. A total of 206 articles were included. Living donors can be divided into those who donate to an emotionally or genetically related person, the so-called directed donors, or to an emotionally or genetically unrelated recipient, the so-called nondirected donors. The most commonly investigated (bio)psychosocial outcome after living donation was health-related quality of life. Other generic (bio)psychological outcomes include specific aspects of mental health such as depression, and fatigue and pain. Social outcomes include financial and employment burdens and problems with insurance. Donation-specific psychosocial outcomes include regret, satisfaction, feelings of abandonment and unmet needs, and benefits of living kidney donation. The experience of living donation is complex and multifaceted, reflected in the co-occurrence of both benefits and burden after donation. Noticeably, no interventions have been developed to improve mid- or long-term psychosocial outcomes among living donors. We highlight areas for methodological improvement and identified 3 areas requiring immediate attention from the transplant community in both research and clinical care: (1) recognizing and providing care for the minority of donors who have poorer long-term psychosocial outcomes after donation, (2) minimizing donation-related financial burden, and (3) studying interventions to minimize long-term psychosocial problems.</p

Hypertension during Pregnancy is Associated with Coronary Artery Calcium Independent of Renal Function

Abstract Background: Hypertension during pregnancy (HDP) increases the risk of future coronary heart disease (CHD), but it is unknown whether this association is mediated by renal injury. Reduced renal function is both a complication of HDP and a risk factor for CHD. Methods: Logistic regression models were fit to examine the association between a history of HDP and the presence and extent of coronary artery calcification (CAC), a measure of subclinical coronary artery atherosclerosis, in 498 women from the Epidemiology of Coronary Artery Calcification Study (mean age 63.3+/-9.3 years). Results: Fifty-two (10.4%) women reported a history of HDP. After adjusting for age at time of study participation, HDP was associated with increased serum creatinine later in life (p=0.014). HDP was positively associated with the presence of CAC after adjusting for age at time of study participation (OR=2.7, 95% CI 1.4-5.4). This association was slightly attenuated with adjustment for body size and blood pressure (OR=2.4, 95% CI 1.2-4.9) but was not further attenuated with adjustment for serum creatinine and urinary albumin/creatinine ratio (OR=2.6, 95% CI 1.3-5.3). Results were similar for CAC extent. Conclusions: HDP may increase a woman's risk of future CHD beyond traditional risk factors and renal function. Women with a history of HDP should be monitored for potential increased risk of CHD as they age.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78144/1/jwh.2008.1285.pd

Incorporating Cystatin C to Predict Methotrexate Elimination in Patients with CNS Lymphoma and Suspicious Renal Function

High-dose methotrexate (MTX; ≥1 g/m2) is a renally eliminated and nephrotoxic first-line therapy for central nervous system (CNS) lymphoma. Creatinine-based estimation of renal function is the recommended approach to dosing MTX in these cases, but nonrenal determinants of creatinine production and elimination in cancer patients such as malnutrition and cachexia lead to overestimation of glomerular filtration rate (GFR) by this method and a heightened risk for drug toxicity. Serum cystatin C is one of the first readily available, relatively inexpensive, endogenous biomarkers to emerge as a practical adjunct to creatinine for estimation of renal function for drug dosing. In this report, we describe two cases where cystatin C was used in conjunction with creatinine to inform MTX dosing for CNS lymphoma. In both cases, the estimated GFR was nearly 40% lower with the combination of the two biomarkers compared to creatinine-only estimates. Empiric MTX dose reductions as a product of these results likely spared the patients sustained exposure to toxic drug concentrations and facilitated earlier administration of supportive care interventions. Further prospective investigations with validated dosing regimens including cystatin C are warranted for high-dose MTX

Clinical and kidney structural characteristics of living kidney donors with nephrolithiasis and their long-term outcomes

Background: Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function. Methods: We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (\u3e5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including review of metabolic evaluations in stone formers. Long-term risks of renal complications (low eGFR and hypertension) by stone former status were evaluated. Results: There were 12 symptomatic and 76 asymptomatic stone formers among 866 donors. Overall, baseline clinical characteristics and implantation biopsy findings were similar between stone formers and non-stone formers. After a median follow-up of 10 y, stone former status was not associated with eGFR \u3c60 mL/min/1.73 m2, eGFR \u3c45 mL/min/1.73 m Conclusions: Both asymptomatic and symptomatic SF have favorable histology findings at baseline. Long-term kidney outcomes were favorable in select stone formers with no evident increased long-term risk for decreased kidney function or hypertension after donation

Early chronic kidney disease: diagnosis, management and models of care

Chronic kidney disease (CKD) is prevalent in many countries, and the costs associated with the care of patients with end-stage renal disease (ESRD) are estimated to exceed US$1 trillion globally. The clinical and economic rationale for the design of timely and appropriate health system responses to limit the progression of CKD to ESRD is clear. Clinical care might improve if early-stage CKD with risk of progression to ESRD is differentiated from early-stage CKD that is unlikely to advance. The diagnostic tests that are currently used for CKD exhibit key limitations; therefore, additional research is required to increase awareness of the risk factors for CKD progression. Systems modelling can be used to evaluate the impact of different care models on CKD outcomes and costs. The US Indian Health Service has demonstrated that an integrated, system-wide approach can produce notable benefits on cardiovascular and renal health outcomes. Economic and clinical improvements might, therefore, be possible if CKD is reconceptualized as a part of primary care. This Review discusses which early CKD interventions are appropriate, the optimum time to provide clinical care, and the most suitable model of care to adopt