Ngan N. Lam

Cardiovascular disease in kidney donors: matched cohort study

Objective To determine whether people who donate a kidney have an increased risk of cardiovascular disease. Design Retrospective population based matched cohort study. Participants All people who were carefully selected to become a living kidney donor in the province of Ontario, Canada, between 1992 and 2009. The information in donor charts was manually reviewed and linked to provincial healthcare databases. Matched non-donors were selected from the healthiest segment of the general population. A total of 2028 donors and 20u2009280 matched non-donors were followed for a median of 6.5 years (maximum 17.7 years). Median age was 43 at the time of donation (interquartile range 34-50) and 50 at the time of follow-up (42-58). Main outcome measures The primary outcome was a composite of time to death or first major cardiovascular event. The secondary outcome was time to first major cardiovascular event censored for death. Results The risk of the primary outcome of death and major cardiovascular events was lower in donors than in non-donors (2.8 v 4.1 events per 1000 person years; hazard ratio 0.66, 95% confidence interval 0.48 to 0.90). The risk of major cardiovascular events censored for death was no different in donors than in non-donors (1.7 v 2.0 events per 1000 person years; 0.85, 0.57 to 1.27). Results were similar in all sensitivity analyses. Older age and lower income were associated with a higher risk of death and major cardiovascular events in both donors and non-donors when each group was analysed separately. Conclusions The risk of major cardiovascular events in donors is no higher in the first decade after kidney donation compared with a similarly healthy segment of the general population. While we will continue to follow people in this study, these interim results add to the evidence base supporting the safety of the practice among carefully selected donors.

Risk of Acute Kidney Injury From Oral Acyclovir: A Population-Based Study

BACKGROUNDnIntravenous acyclovir-induced acute kidney injury (AKI) from drug crystallization in the renal tubules is described in case reports, review articles, and drug prescribing manuals. Similarly, AKI from oral acyclovir is described in case reports, but the risk in routine practice is unknown.nnnSTUDY DESIGNnRetrospective population-based cohort study.nnnSETTING & PARTICIPANTSnWe studied a large cohort of older patients in Ontario, Canada, receiving new outpatient prescriptions from 1997 to 2011 for oral acyclovir or valacyclovir (which is metabolized to acyclovir). The comparison drug was famciclovir, an antiviral used for indications similar to acyclovir, but with no known renal toxicity.nnnPREDICTORnOutpatient prescription for oral acyclovir, valacyclovir, or famciclovir.nnnOUTCOMESnThe primary outcome was hospital admission with AKI in the 30 days after the initial prescription.nnnMEASUREMENTSnWe assessed the primary outcome with health care diagnostic codes. In a subpopulation, we assessed AKI using available laboratory serum creatinine measurements.nnnRESULTSn76,269 patients received acyclovir or valacyclovir and 84,646 received famciclovir. On average, patients were aged 76 [IQR, 71-81] years and prescription duration was 7 days. Acyclovir or valacyclovir use was not associated with a higher risk of hospital admission with AKI (209 [0.27%] events with acyclovir or valacyclovir vs 238 [0.28%] events with famciclovir [relative risk, 0.97; 95% CI, 0.81-1.17]). Results were consistent in adjusted analyses, in all subgroups, and in the subpopulation with laboratory measurements.nnnLIMITATIONSnDiagnostic codes had high specificity but low sensitivity and underestimated the incidence of AKI. Only a limited number of patients (n = 2,729) had serum creatinine values available.nnnCONCLUSIONSnIn this population-based study of older adults, oral acyclovir use was not associated with a higher risk of AKI compared to famciclovir.

Long-term medical risks to the living kidney donor.

Living kidney donation benefits recipients and society but carries short-term and long-term risks for the donor. This Review summarizes the studies that underlie our current understanding of these risks in the first decade after donation, with a view to improving the informed consent process. Two studies report a higher risk of end-stage renal disease (ESRD) among donors than among healthy nondonors; however, the absolute 15-year incidence of ESRD is <1%. All-cause mortality and the risk of cardiovascular events are similar among donors and healthy nondonors, although one study provides evidence for a 5% increase in all-cause mortality after 25 years that is attributable to donation. Some evidence suggests that the 20-year incidence of gout is slightly higher among donors than among healthy nondonors. The risks of gestational hypertension or pre-eclampsia seem to be 6% higher in pregnancies among donors than in pregnancies among healthy nondonors. The incidences of acute kidney injury, kidney stones that require surgical intervention, gastrointestinal bleeding and fractures seem no higher among donors than among healthy nondonors, although some of these conclusions are based on a small number of events. Future studies must clarify the lifetime incidence of long-term outcomes, particularly in relation to a donors age, race, and history of comorbidities.

Acute dialysis risk in living kidney donors

It is crucial to carefully screen donors and essential to resist compromises. If this is respected the survival, the co-morbidity, ESRD or even acute renal failure, as shown by Lam et al. in the current issue of this journal, appear to be similar to those in the general population.

Risk of kidney stones with surgical intervention in living kidney donors.

A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20u2009190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow‐up time was 8.4 years (maximum 19.7 years; loss to follow‐up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7u2009events/10u2009000u2009person‐years; rate ratio 0.85; 95% confidence interval [CI] 0.47–1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1u2009events/10u2009000u2009person‐years; rate ratio 0.75; 95% CI 0.45–1.24). These interim results are reassuring for the safety of living kidney donation.

Gout After Living Kidney Donation: A Matched Cohort Study

BACKGROUNDnIn the general population, high serum uric acid concentration is a risk factor for gout. It is unknown whether donating a kidney increases a living donors risk of gout as serum uric acid concentration increases in donors after nephrectomy.nnnSTUDY DESIGNnRetrospective matched cohort study using large health care databases.nnnSETTING & PARTICIPANTSnWe studied living kidney donors who donated in 1992 to 2010 in Ontario, Canada. Matched nondonors were selected from the healthiest segment of the general population. 1,988 donors and 19,880 matched nondonors were followed up for a median of 8.4 (maximum, 20.8) years.nnnPREDICTORnLiving kidney donor nephrectomy.nnnOUTCOMESnThe primary outcome was time to a diagnosis of gout. The secondary outcome in a subpopulation was receipt of medications typically used to treat gout (allopurinol or colchicine).nnnMEASUREMENTSnWe assessed the primary outcome with health care diagnostic codes.nnnRESULTSnDonors compared with nondonors were more likely to be given a diagnosis of gout (3.4% vs 2.0%; 3.5 vs 2.1 events/1,000 person-years; HR, 1.6; 95% CI, 1.2-2.1; P<0.001). Similarly, donors compared with nondonors were more likely to receive a prescription for allopurinol or colchicine (3.8% vs 1.3%; OR, 3.2; 95% CI, 1.5-6.7; P=0.002). Results were consistent in multiple additional analyses.nnnLIMITATIONSnThe primary outcome was assessed using diagnostic codes in health care databases. Laboratory values for serum uric acid and creatinine in follow-up were not available in our data sources.nnnCONCLUSIONSnThe findings suggest that donating a kidney modestly increases an individuals absolute long-term incidence of gout. This unique observation should be corroborated in future studies.

Gout after living kidney donation: Correlations with demographic traits and renal complications

Background: The demographic and clinical correlates of gout after living kidney donation are not well described. Methods: Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared the rates of renal diagnoses among donors with and without gout, matched in the ratio 1:3 by age, sex, and race. Results: The study sample of 4,650 donors included 13.1% African Americans. By seven years, African Americans were almost twice as likely to develop gout as Caucasian donors (4.4 vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval (CI) 1.0-3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86; 95% CI 0.66-1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5-107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1-11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2-4.2). Conclusion: Donor subgroups at increased risk of gout include African Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment.

Risk of serious gastrointestinal bleeding in living kidney donors

Individuals with moderate‐to‐severe reduced renal function have greater risk of gastrointestinal bleeding than those with normal renal function. We conducted a retrospective matched cohort study to assess whether living kidney donors share a similar risk. We reviewed pre‐donation charts for living kidney donations from 1992 to 2009 in Ontario, Canada, and linked this information to healthcare databases. We selected healthy non‐donors from the general population and matched ten non‐donors to every donor. Of the 2009 donors and 20 090 matched non‐donors, none had evidence of gastrointestinal bleeding prior to cohort entry. The cohort was followed for a median of 8.4 yr (maximum 19.7 yr; loss to follow‐up <7%). There was no significant difference in the rate of hospitalization with gastrointestinal bleeding in donors compared to non‐donors (18.5 vs. 14.9 events per 10 000 person‐years; rate ratio 1.24; 95% confidence interval [CI] 0.85–1.81). Similar results were obtained when we assessed the time to first hospitalization with gastrointestinal bleeding (hazard ratio 1.25, 95% CI 0.87–1.79). In conclusion, we found living kidney donation was not associated with a higher risk of hospitalization with gastrointestinal bleeding. These results are reassuring for the safety of the practice.

Results of a randomized controlled trial on statin use in dialysis patients had no influence on statin prescription.

Randomized trials provide high-quality evidence for patient care. The Der Deutsche Diabetes Dialyse Studie (4D), a randomized study which demonstrated no benefit of statins among diabetic patients receiving hemodialysis, was published in July 2005. To determine effects of this study we conducted a retrospective, population-based, time series analysis with change-point regression to see if the rate of statin prescription to dialysis patients had been modified. We linked health administrative data for all diabetic hemodialysis patients living in Ontario, Canada, with similar characteristics to the 4D patient cohort. During the nearly 11-year period prior to study publication, the rate of statin use increased almost 14-fold, from 43 to 597 per 1000 patients. For 2.5 years after study publication, rather than diminish, statin use continued to rise to an absolute rate of 676 per 1000 patients. These temporal patterns in statin use closely mimicked trends in the diabetic population not receiving dialysis. The 4D trial had no impact on statin use when we restricted the analysis to incident statin prescriptions or expanded the characteristics of the dialysis patients considered for study. Thus, we found that publication of a large, expensive, randomized controlled trial in patients receiving hemodialysis had no immediate impact on clinical practice. The use of a common cardiovascular medication in this patient population appears to be influenced by other factors.

Associations of pre-transplant prescription narcotic use with clinical complications after kidney transplantation.

Background: The impact of narcotic use before kidney transplantation on post-transplant clinical outcomes is not well described. Methods: We examined integrated national transplant registry, pharmacy records, and Medicare billing claims to follow 16,322 kidney transplant recipients, of whom 28.3% filled a narcotic prescription in the year before transplantation. Opioid analgesic fills were normalized to morphine equivalents (ME) and expressed as mg/kg exposures (approximate quartiles: 0.1-1.7, 1.8-5.4, 5.5-23.7, and ≥23.8 mg/kg, respectively). Post-transplant cardiovascular, respiratory, neurological, accidents, substance abuse, and noncompliance events were identified using diagnosis codes on Medicare billing claims. Adjusted associations of ME level with post-transplant complications were quantified by multivariate Cox regression. Results: The incidence of complications at 3 years post-transplant among those with the highest pre-transplant ME exposure compared to no use included: ventricular arrhythmias, 1.1 vs. 0.2% (p < 0.001); cardiac arrest, 4.7 vs. 2.7% (p < 0.05); hypotension, 14 vs. 8% (p < 0.0001); hypercapnia, 1.6 vs. 0.9% (p < 0.05); mental status changes, 5.3 vs. 2.7% (p < 0.001); drug abuse/dependence, 7.0 vs. 1.7% (p < 0.0001); alcohol abuse, 1.8 vs. 0.6% (p = 0.0001); accidents, 0.9 vs. 0.3% (p < 0.05); and noncompliance, 3.5 vs. 2.3% (p < 0.05). In multivariate analyses, transplant recipients with the highest level of pre-transplant narcotic use had approximately 2 to 4 times the risks of post-transplant ventricular arrhythmias, mental status changes, drug abuse, alcohol abuse, and accidents compared with non-users, and 35-45% higher risks of cardiac arrest and hypotension. Conclusion: Although associations may reflect underlying conditions or behaviors, high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation.