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Native Nephrectomy with Renal Transplantation Decreases Hypertension Medication Requirements in Autosomal Dominant Polycystic Kidney Disease
| Content Provider | Semantic Scholar |
|---|---|
| Author | Shumate, Ashley M. Bahler, Clinton D. Goggins, William C. Sharfuddin, Asif A. Sundaram, Chandru |
| Copyright Year | 2016 |
| Abstract | Background: In autosomal dominant polycystic kidney disease(ADPKD), hypertension(HTN) is the most prevalent complication and plays an essential role in morbidity and progression of chronic kidney disease(CKD). Objective: To assess control of HTN following native nephrectomy(Nx) and renal transplant recipients with ADPKD. Design, Setting, and Participants: Blood pressure control was studied retrospectively in 144 ADPKD patients who underwent renal transplantation between 2003 and 2013. Intervention: Renal transplantation alone(n=67) versus renal transplantation with concurrent ipsilateral Nx(n=40) versus renal transplantation with concurrent ipsilateral Nx and delayed contralateral nephrectomy(n=37) Outcome Measurements and Statistical Analysis: The primary outcome was change in quantity and defined daily dose(DDD) of antihypertensive medications after renal transplantation. Predictors of DDD at 36months were assessed using a multivariable linear regression model. Results and Limitations: Comparing pre-operative to post-operative medications at 12, 24, and 36months follow-up, transplantation with concurrent ipsilateral Nx had a greater decrease in quantity(-1.2 vs -0.5medications, p=0.008; -1.1 vs -0.3, p=0.007; and -1.2 vs -0.4, p=0.03) and DDD(-3.3 vs -1.0, p=0.0008; -2.9 vs -1.0, p=0.006; and 2.7 vs -0.6, p=0.007) of antihypertensives than transplantation alone, respectively. There was a significant decrease in quantity(p=0.0005) and DDD (p=0.009) of medications from post-ipsilateral to 12months post-contralateral Nx. Limitations included retrospective design and inability to correlate blood pressure measurements with antihypertensive medication changes. Conclusion: In ADPKD patients undergoing renal transplantation, concurrent ipsilateral native Nx significantly decreases quantity and DDD of antihypertensives. Delayed contralateral native Nx decrease these further. Patient Summary: We examined blood pressure control following kidney transplantation and removal of native kidneys in autosomal dominant polycystic kidney disease patients. Patients with one native kidney removed at time of transplantation required less blood pressure medications than those who had kidney transplantation alone. Patients who had their second native kidney removed at a later surgery required even fewer medications to control blood pressure. INTRODUCTION Autosomal Dominant Polycystic Kidney Disease(ADPKD) is one of the most common renal diseases, affecting 1:400 to 1:1000 people. Among its manifestations, hypertension(HTN) stands out as the most prevalent complication, and is an essential component to the development and progression of both renal disease and morbidity and mortality.[1] HTN in ADPKD occurs early, around age 30, and is the initial presentation for approximately 30% of patients.[2] In approximately 60% of patients, HTN occurs before any impairment of renal function.[3] HTN plays an essential role in morbidity of ADPKD, as cardiovascular complications account for the majority of deaths since renal replacement therapies have become prevalent.[4, 5] Therefore, it is crucial to aggressively control HTN to preserve and improve cardiac and renal function.[6] Once progressive expansion of renal cysts occurs, the massive enlargement of the kidneys and simultaneous shrinkage of normal renal parenchyma eventually leads to renal failure. There is an inverse relationship of renal function and HTN: as renal function declines, the frequency and severity of HTN increases.[7] When end stage renal disease (ESRD) occurs in ADPKD, there is also increased risk of other cardiovascular events.[8] Renal transplantation(Tx) is the treatment of choice for ESRD. Complications after Tx in ADPKD patients are no greater than in the general population.[1] However, despite a functioning renal Tx, the voluminous native kidneys may exert a sustained hypertensive effect. How to properly manage the native kidneys after Tx, and whether or not surgical means are necessary, remains disputed.[9] Few studies have shown how HTN control is affected with surgical intervention for native cystic kidneys. Native nephrectomy (Nx) is occasionally performed at time of renal Tx in ADPKD for refractory pain caused by the cumbersome cystic kidney(s), but has not been well-documented as a potential therapy for HTN. The few studies that have examined how Nx affects HTN have been small or only examined blood pressure control in the perioperative period; however, these studies have shown some improvement from Nx.[9-11] No large study has shown significant improvement or resolution of HTN at long-term follow-up for native Nx with renal Tx in the ADPKD population. Our goal was to evaluate how blood pressure responds long-term to this surgical intervention. Our hypothesis was ipsilateral native Nx at time of renal Tx would decrease required antihypertensives to control blood pressure long-term, and that delayed contralateral native Nx would further decrease antihypertensive requirement. MATERIALS AND METHODS Population Our institution’s transplant and billing databases were searched for patients who carried a diagnosis of ADPKD and had renal Tx between 2003 and 2013. Patients who had Tx alone or Tx with concurrent ipsilateral native Nx were included. Patients were excluded if they had bilateral Nx at time of Tx(n=9), had multi-organ transplant(e.g. liver and kidney, (n=3), were lost to follow-up(n=14), or were deceased within 4 months of Tx(n=4). 144 patients met the inclusion criteria. Institutional review board approval was obtained for this study. The primary outcome was change in quantity and defined daily dose of antihypertensive medications for patients after renal Tx. Patients not being treated with antihypertensive medications at the time of transplantation were excluded from the analysis(n=26). Defined daily dose(DDD) is a means of standardizing and analyzing drug consumption among patients, and was created by the World Health Organization. It is the “assumed average maintenance dose per day for a drug used for its main indication in adults.”[12] Since it can differentiate between different doses of the same medication, DDD provides better representation of drug requirements compared to using the quantity of different medications alone. Patient comorbidities were compared at time of Tx using Charlson Comorbidity Index(CCI).[13] Glomerular filtration rate(GFR) was obtained as an appraisal of renal function, and was calculated using the Modification of Diet in Renal Disease(MDRD) equation.[14] Blood pressure measurements were obtained from clinic notes pre-operatively and through 36 months follow-up. Native Nx at time of renal Tx was performed by the transplant surgeon by an open approach, and the completion native Nx was performed by a urologic surgeon using a laparoscopic approach at a mean of 9.8 months post-Tx. Details of the surgical procedures have been described previously.[15] The standard immunosuppression regimen was early steroid withdrawal(<7 days), and maintenance immunosuppression with tacrolimus and mycophenolate. Statistical analysis Descriptive analysis was performed for demographic data. Student’s T-test was used for continuous variables and Pearson chi-square test for categorical variables. A 2-tailed analysis was performed in all tests. Comparing antihypertensives between postfirst Nx and post-second Nx was done using a paired Student’s T-test. All other analyses were un-paired. The analysis of variance(ANOVA) test was used for GFR at 12, 24, and 36-months postoperatively. Multivariable linear regression was used to determine predictors of DDD of antihypertensives at 36 months. Age, CCI, tobacco use, and BMI were included in the multivariable analysis a priori as they were identified as potential confounders. Nephrectomy status and gender were included in the multivariable analysis due to having a p-value <0.05 on univariable analysis. A priori significance was set at p<0.05 for all analyses. All statistical analyses were performed using Stata 13.1(Stata Corp. LP, College Station, TX). RESULTS Demographic and patient characteristics data can be found in Table 1. At time of Tx, there was no difference between renal Tx alone(Group 1) vs renal Tx with native Nx(Group 2) in mean age, gender, ethnicity, BMI, percentage of patients with diabetes mellitus, percentage of tobacco users, or percentage of patients requiring pre-Tx dialysis. Similarly, no difference was found between groups in number of patients who carried a diagnosis of HTN at Tx. Mean CCI, international ionized ratio, GFR, and albumin were similar between groups at time of Tx. Hemoglobin at time of Tx was slightly lower in Group 1(12.2 g/dL) compared to Group 2(12.8 g/dL),(p=0.02). A comparison of medication requirements between Groups 1 and 2 can be found in Table 2. At time of Tx, quantity of medications was similar between Group 1 and Group 2 (2.3 vs 2.6, p=0.23). There was no difference in DDD between Groups 1 and 2 (3.7 vs 4.4, p=0.27) at time of Tx. Results of medication requirements after ipsilateral and delayed contralateral nephrectomy can be found in Figures 1 and 2. At 4 months post-Tx, the mean quantity of medications required to control blood pressure was significantly less in Group 2 compared to Group 1 (1.3 vs 1.9, p=0.001). Similarly, DDD of antihypertensives was much lower in Group 2 than Group 1 (1.2 vs 2.7, p<0.0001). Similar to 4 months followup, patients in Group 2 required less quantity of antihypertensives and DDD compared to Group 1 at 8, 12, and 24 months follow-up.. At 36 months, while there was a smaller quantity and DDD of antihypertensives in Group 2, this was only significant in DDD of antihypertensives (p=0.003), not quantity(p=0.16). The mean change in quantity as well as mean change in DDD of antihypertensives was calculated from time of Tx to 12 and 24 months post-Tx for Group 2. These results showed a significant reduction from preto post-Tx in quantity and |
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| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
