May June 2019: Transplantation Abstract Roundup

Renal Transplantation among Patients with ESRD Due to Lupus Nephritis

Annals of Internal Medicine. 2019;170(4):240-247.

Rates of premature death are high among patients with end-stage renal disease (ESRD) due to lupus nephritis (ESRD-LN). April Jorge, MD, and colleagues conducted a nationwide cohort study designed to examine the potential effect on survival of renal transplant among patients with ESRD-LN in the United States.

The study utilized data from the United States Renal Data System to identify patients with incident ESRD-LN who were waitlisted for a renal transplant. First renal transplant was analyzed as a time-varying exposure.

The primary outcomes of interest were all-cause and cause-specific mortality. In the primary analysis, hazard ratios (HRs) for the outcomes were estimated using time-dependent Cox regression analysis. In a secondary analysis limited to patients with Medicare, sequential cohort matching was used to allow assessment of time-varying covariates.

There were 9659 patients with LN-ESRD waitlisted for a renal transplant during the study period; of those, 59% (n=5738) received a transplant. Most (82%) of the eligible patients were female and 60% were nonwhite.

Among the waitlisted patients, there was an association between transplantation and reduced all-cause mortality (adjusted HR, 0.30; 95% confidence interval [CI], 0.27-0.33). Adjusted HRs for cause-specific mortality were 0.26 (95% CI, 0.23-0.30) for cardiovascular disease; 0.30 (95% CI, 0.19-0.48) for coronary heart disease; 0.41 (95% CI, 0.32-0.52) for infection; and 0.41 (95% CI, 0.31-0.53) for sepsis.

“Renal transplant was associated with a survival benefit, primarily due to reduced deaths from cardiovascular disease and infection. The findings highlight the benefit of timely referral for transplant to improve outcomes in this population,” the researchers said.

APOL1 Genotyping May Improve Outcomes in Renal Transplantation

Transplantation. 2019;103(3):487-492

Researchers have gained enhanced understanding of the pathogenesis in apolipoprotein L1 (APOL1) gene-associated chronic kidney disease (CKD) via observations in kidney transplantation. According to Lijun Ma, MD, PhD, and colleagues, the safety of living donor kidney donation in those with recent African ancestry may be improved with APOL1 genotyping. The process may also alter the allocation of deceased kidney donors.

This review outlines the potential mechanisms underlying development of APOL1-associated nephropathy. The article also highlights the roles for circulating APOL1 protein versus intrinsic renal expression of APOL1, as well as the requirement for modifying genetic and/or environmental factors.

In native kidney disease and following renal transplantation, current evidence supports local kidney production of APOL1 renal-risk variant protein in the development of nephropathy. Only a minority of kidneys from individuals with APLO1 high-risk genotypes will develop CKD or manifest shorter renal allograft survival after transplantation, making it important to identify modifying factors that explain why only a subset of kidneys develop nephropathy. It is likely that environmental exposures, rather than major APOL1-second gene interactions, will be stronger modifiers of the risk for nephropathy.

In conclusion, the researchers said, “The evolving understanding of the pathogenesis in APOL1-associated nephropathy will identify biomarkers predicting nephropathy in individuals at high genetic risk and lead to novel therapies to prevent or slow native CKD progression and prolong survival of transplanted kidneys. In the interim, the National Institutes of Health–sponsored APOL1 Long-Term Kidney Transplantation Outcomes Network will determine whether APOL1 genotyping in individuals with recent African ancestry improves outcomes and safety in kidney transplantation.”

Office Blood Pressure versus 24-Hour Ambulatory Blood Pressure Measurements

Nephrology Dialysis Transplantation. doi.org/10.1093/ndt/gfy355

Patients who have undergone renal transplantation have a high prevalence of nocturnal hypertension. In addition, hypertension misclassification by office blood pressure is common in this patient population. There are no available data on the impact of hypertension misclassification by office blood pressure on the management of blood pressure these patients.

Francesca Mallamaci, MD, and colleagues conducted a longitudinal study that included 260 clinically stable patients. A total of 785 paired office and 24-hour ambulatory blood pressure monitoring measurements over a median follow-up of 3.9 years were available in the total cohort.

Of the 260 patients, 74% had nocturnal hypertension, defined as >102/70 mmHg. Over the follow-up period, the average office blood pressure and the 24-hour ambulatory blood pressure remained stable, as did the prevalence of nocturnal hypertension (77% at the final observation). However, the global agreement between office blood pressure and average 24-hour, daytime, and night-time blood pressure was unsatisfactory (k-statistics 0.10-0.26). In 25% of all visits (n=193) where office blood pressure indicated the need of initiation of antihypertensive therapy or modification (blood pressure >140/90 mmHg), the 24-hour ambulatory blood pressure was actually normal (<130/80 mm Hg). In 12% of visits (n=94), 24-hour ambulatory blood pressure was in the hypertensive range while office blood pressure was normal. In all, office blood pressure provided misleading therapeutic indication in 37% of visits.

In summary, the researchers said, “Hypertension misclassification by office blood pressure is a common phenomenon in stable renal transplant patients on long-term follow-up. Office blood pressure may lead to inappropriate therapeutic decisions in over one-third of follow-up visits in these patients.”