Hypertension Management in Patients with Chronic Kidney Disease.

Hypertension and chronic kidney disease are closely linked. Patients with chronic kidney disease have hypertension almost universally and uncontrolled hypertension accelerates the decline in kidney function. The pathophysiology of hypertension in chronic kidney disease is complex, but is largely related to reduced nephron mass, sympathetic nervous system overactivation, involvement of the renin-angiotensin-aldosterone system, and generalized endothelial dysfunction. Consensus guidelines for blood pressure targets have adopted a blood pressure <120/80 mm Hg in native chronic kidney disease and <130/80 mm Hg in kidney transplant recipients. Guidelines also strongly advocate for renin-angiotensin-aldosterone system blockade as the first-line therapy.

Outcomes of kidney donors with sickle cell trait: A preliminary analysis.

Most transplant centers do not screen kidney donor candidates for sickle cell trait (SCT) and many decline candidates with SCT since it may associate with kidney disease. We compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure. The prevalence of SCT in African American (AA) donors was 11 per 1000 compared to 73 per 1000 in non-donor AA. Donors with SCT were younger; 33 versus 35 years in controls, nine were AA, six were White, and two were listed as other or unknown ethnicities. After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive, developed hypertension or cardiovascular disease were similar. No donor with SCT developed an eGFR <30 mL/min/1.73 m2 or kidney failure. SCT was, however, associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 - 22.7), P = .01. This small and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort of donors with SCT.

Outcomes of Kidney Donors With Impaired Fasting Glucose.

BACKGROUND: Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney. METHODS: We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG): <100 mg/dL (n = 6204), 100-125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250). RESULTS: Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG <126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04). CONCLUSIONS: Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.

Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney Donors.

BACKGROUND: Obesity is associated with the two archetypal kidney disease risk factors: hypertension and diabetes. Concerns that the effects of diabetes and hypertension in obese kidney donors might be magnified in their remaining kidney have led to the exclusion of many obese candidates from kidney donation. METHODS: We compared mortality, diabetes, hypertension, proteinuria, reduced eGFR and its trajectory, and the development of kidney failure in 8583 kidney donors, according to body mass index (BMI). The study included 6822 individuals with a BMI of <30 kg/m2, 1338 with a BMI of 30-34.9 kg/m2, and 423 with a BMI of ≥35 kg/m2. We used Cox regression models, adjusting for baseline covariates only, and models adjusting for postdonation diabetes, hypertension, and kidney failure as time-varying covariates. RESULTS: Obese donors were more likely than nonobese donors to develop diabetes, hypertension, and proteinuria. The increase in eGFR in obese versus nonobese donors was significantly higher in the first 10 years (3.5 ml/min per 1.73m2 per year versus 2.4 ml/min per 1.73m2 per year; P<0.001), but comparable thereafter. At a mean±SD follow-up of 19.3±10.3 years after donation, 31 (0.5%) nonobese and 12 (0.7%) obese donors developed ESKD. Of the 12 patients with ESKD in obese donors, 10 occurred in 1445 White donors who were related to the recipient (0.9%). Risk of death in obese donors was not significantly increased compared with nonobese donors. CONCLUSIONS: Obesity in kidney donors, as in nondonors, is associated with increased risk of developing diabetes and hypertension. The absolute risk of ESKD is small and the risk of death is comparable to that of nonobese donors.

Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Definitions.

INTRODUCTION: As many as 50% of U.S. transplant centers do not accept kidney donor candidates with hypertension, citing the link between hypertension, kidney disease, and cardiovascular disease (CVD). METHODS: We ascertained mortality, CVD, proteinuria, estimated glomerular filtration rate (eGFR) trajectory, reduced eGFR, and end-stage kidney disease (ESKD) in 904 hypertensive donors (blood pressure [BP] ≥140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90 mm Hg. RESULTS: Hypertensive donors were older, 58.1% were <50 years of age, and they had a lower eGFR. The majority were white and related to their recipient. At the end of follow-up, 14.3 ± 10.1 years (range 4-48 years) from donation, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes. The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors. eGFR slope over time was similar in hypertensive and nonhypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 ± 10.3 years after donation (adjusted hazard ratio 1.14 [95% confidence interval 0.62-2.12], P = 0.67). Sensitivity analysis using the new definition of hypertension (≥130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes. CONCLUSIONS: Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.

Long-term outcomes of kidney donors with fibromuscular dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) is a non-atherosclerotic systemic arterial disease that is not infrequently discovered during kidney donor evaluation. Current guidelines do not provide recommendations regarding the use of kidneys from donors with FMD and there is a paucity of data on the outcomes of these donors. METHODS: The Renal and Lung Living Donor Evaluation (RELIVE) study addressed long-term outcomes of 8922 kidney donors who donated between 1963 and 2007. We compared the development of hypertension, cardiovascular disease (CVD), proteinuria and reduced estimated glomerular filtration rate (eGFR) in 113 kidney donors with FMD discovered during donor evaluation versus 452 propensity score matched donors without FMD. Outcomes modeling with logistic and Cox regression analysis and Kaplan-Meier statistics were performed. RESULTS: Donors with FMD were older (51 versus 39 years), were more likely to be women (80% versus 56%) and had a higher systolic blood pressure at donation (124.7 versus 121.3 mmHg) (P < 0.05 for all). After a mean ± standard deviation follow-up of 15.5 ± 8.9 years, a similar proportion of donors with and without FMD were alive, and developed hypertension (22.2% versus 19.8%), proteinuria (20.6% versus 13.7%) and CVD (13.3% versus 13.5%). No donor with FMD developed an eGFR <30 mL/min/1.73 m2 or end-stage kidney disease. The multivariable risk of mortality, CVD and renal outcomes in donors with FMD was not elevated. CONCLUSIONS: Kidney donors with FMD appear to do well, do not appear to incur increased risks of hypertension, proteinuria, CVD or reduced eGFR, and perhaps carefully selected candidates with FMD can safely donate as long as involvement of other vascular beds is ruled out.

Outcomes of kidney donors with pre- and post-donation kidney stones.

Roughly 25% of US transplant centers exclude donor candidates with kidney stones fearing future obstructive consequences and the possible association between stones and CKD. We compared the development of hypertension, proteinuria, and reduced eGFR in 227 kidney donors with kidney stones to 908 propensity score-matched donor controls without kidney stones using data from The Renal and Lung Donor Evaluation (RELIVE) Study which studied intermediate and long-term outcomes of 8922 donors who donated between 1963 and 2007. 200 donors had kidney stones prior to donation, 21 had post-donation stones, and 6 had pre- and post-donation stones. Donors with stones were older, more likely to be Caucasian, less likely to be related to the recipient and had a higher fasting glucose. After 16.5 ± 10.9 years (range 0-44 years) from donation to study close, no ESKD occurred in donors with stones. The multivariable risks of hypertension, proteinuria, and reduced GFR were similar in donors with and without kidney stones. We could not demonstrate an association between stones and adverse renal outcomes in kidney donors, and the occurrence of post-donation stones was distinctly rare. These data may provide a rationale for possibly a wider acceptance of donor candidates with low kidney stones burden.

Renal Consequences of COVID-19.

The column in this issue is provided by Sean A. Hebert, MD, assistant professor of Clinical Medicine at the Houston Methodist Academic Institute. Dr. Hebert specializes in transplant nephrology at Houston Methodist.

Special Considerations in Pediatric Kidney Transplantation.

Universally accepted as the treatment of choice for children needing renal replacement therapy, kidney transplantation affords children the opportunity for an improved quality of life over dialysis therapy. Immunologic and surgical advances over the last 15 years have improved the pediatric patient and kidney graft survival. Unique to pediatrics, congenital genitourinary anomalies are the most common primary diseases leading to kidney failure, many with urological issues. Early urological evaluation for post-transplant bladder dysfunction and emphasis on immunization adherence are the mainstays of pediatric pretransplant and post-transplant evaluations. A child's height can be challenging, sometimes requiring an intra-abdominally placed graft, particularly if the patient is <20 kg. Maintenance immunosuppression regimens are similar to adult kidney graft recipients, although distinctive pharmacokinetics may change dosing intervals in children from twice a day to thrice a day. Viral infections and secondary malignancies are problematic for children relative to adults. Current trends to reduce/remove corticosteroid therapy from post-transplant protocols have produced improved linear growth with less steroid toxicity; although these studies are still ongoing, graft function and survival are considered acceptable. Finally, all children with a kidney transplant need a smooth transition to adult clinics. Future research in pertinent psychosocial aspects and continued technological advances will only serve to optimize the transition process. Although some aspects of kidney transplantation are similar in children and adults, for instance immunosuppression and immunosuppressive regimens, and rejection mechanisms and their diagnosis using the Banff criteria, there are important differences this review will focus on and which continue to drive innovation.

Office blood pressure measurement alone often misclassifies treatment status in children with primary hypertension.

OBJECTIVE: Clinicians frequently rely on office blood pressure (BP) measurements alone to assess hypertension control, despite widespread acceptance of 24-h ambulatory blood pressure monitoring (ABPM) as the reference standard in the initial diagnosis of hypertension. This study was designed to investigate how often the hypertensive status differed between concurrent office BP versus ABPM measurements, and whether any patient-specific characteristics predict the risk for misclassification by office BP. PARTICIPANTS AND METHODS: This study evaluated 42 children with primary hypertension who underwent repeated ambulatory monitoring (190 total recordings) with concurrent office BP measurement as part of their participation in n-of-1 trials. RESULTS: In nearly 40% of the visits, the treatment status by office measurement was opposite to the status by ambulatory monitoring. Office BP underestimated the ambulatory hypertensive status (masked uncontrolled hypertension) in 25% of visits and overestimated ambulatory BP (white coat effect) in 14% of visits. The difference between office BP and ambulatory monitoring was consistent within patients across repeated visits. Patients whose office measurement underestimated or overestimated the ambulatory BP at the first visit were more likely to show persistent discrepancy at subsequent visits. CONCLUSION: The underuse of ambulatory monitoring in management decisions of children treated for primary hypertension may result in systematic misclassification of hypertension control.

Thrombotic microangiopathy associated with Valproic acid toxicity.

BACKGROUND: Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA. We present the first case of a patient meeting clinical criteria for DI-TMA following admission for valproic acid toxicity. CASE PRESENTATION: An adolescent male with difficult to control epilepsy was admitted for impaired hepatic function while on valproic acid therapy. On the third hospital day, he developed severe metabolic lactic acidosis and multiorgan failure, prompting transfer to the pediatric intensive care unit. Progressive anemia and thrombocytopenia instigated an evaluation for thrombotic microangiopathy, where confirmed by concomitant hemolysis, elevated lactate dehydrogenase (LDH), low haptoglobin, and concurrent oliguric acute kidney injury. Thrombotic thrombocytopenic purpura was less likely with adequate ADAMTS13. Discontinuing valproic acid reversed the anemia, thrombocytopenia, and normalized the LDH and haptoglobin, supporting a drug-induced cause for the TMA. CONCLUSION: To the best of our knowledge, this is the first report of drug-induced TMA from valproic acid toxicity.