Long-term renal survival in HIV-associated nephropathy with angiotensin-converting enzyme inhibition

BACKGROUND: Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the most common cause of end-stage renal disease (ESRD) in HIV-infected patients. Angiotensin-converting enzyme (ACE) inhibition has previously shown a short-term benefit in HIVAN. This study examines the long-term effects of ACE inhibition on renal survival in HIVAN. METHODS: In this single-center prospective cohort study, 44 patients with biopsy-proven HIVAN were enrolled prior to the onset of severe renal insufficiency (serum creatinine or=two antiviral drugs for >or=30 consecutive days, CD4 lymphocyte count, initial median serum creatinine concentration, or proteinuria. Risk of renal failure was reduced with ACE inhibitors (RR = 0.003, P < 0.0001). Exposure to antiretroviral therapy did not have a significant impact on the risk of renal failure. Of the ACE inhibitor-treated group, 87.5% survived compared with 21.4% of the control group (P < 0.001). CONCLUSION: ACE inhibition initiated prior to severe renal insufficiency may offer long-term renal survival benefits in HIVAN. Diagnosis should be sought early in patients with clinical signs suggestive of HIVAN.     

Human immunodeficiency virus infection in end-stage renal disease patients

Human immunodeficiency virus (HIV) infection in patients with end-stage renal disease (ESRD) offers many diagnostic and therapeutic challenges to nephrologists. Renal failure may be a direct consequence of viral infection (HIV-associated nephropathy), or intrinsic renal diseases may occur in previously infected individuals. Patients receiving renal replacement therapy (RRT) may acquire HIV infection from blood transfusions, renal allografts, sexual contacts, or needle sharing by drug addicts. In the early 1980s, the overall prognosis of patients with the acquired immunodeficiency syndrome (AIDS) was very poor, and survival of those with ESRD was dismal. Consequently many even questioned the value of providing maintenance dialysis to patients with AIDS. With advances in diagnostic techniques in serologic and viral markers of disease, and deployment of highly effective antiretroviral agents, the prognosis of HIV-infected patients has dramatically improved. Over the past two decades, experiences in the management of HIV patients with ESRD is accumulating. Both peritoneal dialysis and hemodialysis are effective modes of therapy and many centers are now beginning to perform renal transplantation in HIV-infected patients. This article deals with various aspects of HIV infection in patients with ESRD.     

The clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis

BACKGROUND: Human immunodeficiency virus (HIV)-related renal disease is the third leading cause of end-stage renal disease (ESRD) among African Americans aged 24 to 60 years. This study describes the clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis to define the clinical needs of this growing population. METHODS: Demographic and clinical information was collected on all HIV-infected patients incident to dialysis after January 1, 1998 until January 1, 2001 at five medical centers. The cohort was described overall and by subgroups based on hepatitis status, CD4 lymphocyte count, and use of antiretroviral therapy. Continuous and categoric variables were compared using either the Wilcoxon rank sum or Student t test and Fisher's exact or chi-square tests, as appropriate. RESULTS: A total of 89 patients were included, 55 of whom were alive at the time of data collection. The mean age was 44.6 years (range, 22.7 to 66.9 years), 74.2% were male, and 83.2% patients were African Americans. While only 45.9% of patients undergoing renal biopsy were diagnosed with HIV-associated nephropathy (HIVAN), the majority of patients who had not undergone biopsy carried the clinical diagnosis of HIVAN (69.8%, P = 0.03). Of the cohort, 19.7% tested hepatitis B surface antigen positive, and 67.1% had reactive antibody tests for hepatitis C. Patients with hepatitis C were more likely to have experienced intravenous drug use as a risk behavior for HIV acquisition (OR 8.2; 95% CI 2.39, 27.9; P = 0.001] and to be older (OR 1.1 per year of age; 95% CI 1.02, 1.2; P = 0.01). A total of 60.7% of patients were receiving antiretroviral medication at last follow-up. Among patients alive and receiving antiretroviral medications at the time of data collection, absolute CD4+ count rose (268 vs. 339 cells/mL, P = 0.03), while among patients alive, but not receiving antiretroviral medications, absolute CD4+ count did not change (389 vs. 392 cells/mL, P = 0.11) during similar periods of follow-up. No difference was seen between initial and current HIV RNA levels for either group. Among patients receiving antiretroviral medications, there were significant variations in dosing regimens. The greatest variation was seen in the prescribing patterns of lamivudine with a 12-fold difference among patients. CONCLUSION: The projected growth of the HIV-infected ESRD population requires a better understanding of the clinical needs of this population. The high prevalence of coinfection with hepatitis C as well as the wide variations in dosing patterns for antiretroviral medications are areas that require further investigation to minimize morbidity and mortality among this group.     

Kidney transplantation and waiting list for renal transplantation for human immunodeficiency virus patients

Introduction

The aim of this study was to evaluate the experience of a renal transplantation unit in the management of human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD).

Methods

A prospective study was performed between 2005 and 2010 among 23 patients with ESRD.

Results

In this study 83% of HIV- infected patients with ESRD were included on the waiting list for renal transplantation with 4 patients in a clinical evaluation phase. During the follow-up, 52% of waiting list patients (n = 11) received a renal transplant, and 1 patient underwent a simultaneous kidney-pancreas transplantation. Among the waiting list group we observed a significant later exclusion (43%; n = 3). Among the transplanted group there was a high but clinically inconsequential prevalence of acute tubular necrosis (36%; n = 4) and acute rejection episodes (36%; n = 4). The renal function showed a serum creatinine of 1.1 mg/dL at a follow-up of 24 + 12 months. All patients on the waiting list and after the transplantation are prescribed combined antiretroviral treatment (cART) with a low viral load <50 with CD4 >200.

Conclusions

HIV-infected patients with ESRD should be considered to be candidates for renal transplantation if they meet the HIV inclusion criteria. Renal transplantation in adequately selected HIV-infected patients is a safe procedure with acceptable patient and graft survivals.     

HIV-associated nephropathy: an urban epidemic.

Human immunodeficiency virus-associated nephropathy (HIVAN) is the most common form of chronic renal disease in HIV-1-seropositive patients. Over 85% of cases of HIVAN occur in African-American patients and it is the third leading cause of ESRD in blacks age 20 to 64. Changes in incidence rates of HIVAN have coincided with changes in AIDS incidence rates. The demographics of the AIDS/HIV-1 epidemic indicate that the risk pool for HIVAN will continue to grow and that urban Nephrology centers will continue to see high rates of HIVAN. In addition, improvements in survival rates of HIV-1-seropositive patients on hemodialysis and improved treatment of HIVAN with highly active antiretroviral therapy (HAART) and angiotensin-converting enzyme (ACE)-inhibitors will result in an increased prevalence of HIVAN in the end-stage renal disease (ESRD) and pre-ESRD patient populations.     

Living-related donor renal transplantation in HIV+ recipients using alemtuzumab preconditioning and steroid-free tacrolimus monotherapy: a single center preliminary experience

BACKGROUND: End-stage renal disease (ESRD) is an increasing problem in patients infected with the human immunodeficiency virus (HIV). The use of highly active antiretroviral therapy (HAART) has decreased the morbidity associated with HIV and has prompted renewed interest in renal transplantation. METHODS: We performed four cases of deceased donor renal transplantation in HIV+ recipients and three cases where laparoscopic live donor nephrectomy (LLDN) was utilized to obtain the kidney for transplantation into living-related HIV+ recipients. In the four deceased donor cases, conventional tacrolimus-based immunosuppression, without antibody induction was used. In the three living-related cases, the immunosuppressive regimen was based on two principles: recipient pretreatment and minimal posttransplant immunosuppression. Alemtuzumab 30 mg (Campath 1-H) was used for preconditioning followed by low-dose tacrolimus monotherapy. RESULTS: Of the four deceased donor cases, one patient continues to have good graft function, and another is not yet on dialysis but has significant graft dysfunction. Rejection was observed in three patients (75%). Infectious complications occurred in one patient (25%), all non-acquired immunodeficiency syndrome (AIDs) defining. In the three living-related cases, all had good graft function, and none have experienced acute rejection. HIV viral loads remain undetectable. CD4 counts are slowly recovering. No infectious or surgical complications occurred. There were no deaths in either group. CONCLUSIONS: These data suggest that living-related donor renal transplantation with steroid-free tacrolimus monotherapy in a "tolerogenic" regimen can be efficacious. However, long-term follow-up is needed to confirm this observation.     

Drug therapy for hypertension in hemodialysis patients

The majority of end-stage renal disease (ESRD) patients are hypertensive. Drug therapy for hypertension in hemodialysis (HD) patients includes all classes of antihypertensive drugs, with the sole exception of diuretics. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers may decrease morbidity and mortality by reducing the mean arterial pressure (MAP), aortic pulse wave velocity, and aortic systolic pressure augmentation, as well as left ventricular hypertrophy (LVH) and probably reduction of C-reactive protein (CRP) and oxidant stress. Potential risk factors include hyperkalemia, anaphylactoid reaction with AN69 membranes (particularly ACE inhibitors), and aggravation of renal anemia. beta-blockers decrease not only mortality, blood pressure (BP), and ventricular arrhythmias, but also improve left ventricular function in ESRD patients. Nonselective beta-blockers can cause an increase in serum potassium (particularly during fasting or exercise). Lisinopril and atenolol have a predominant renal excretion and therefore a prolonged half life in ESRD patients. Thus thrice-weekly supervised administration of these drugs after HD can enhance BP control. The use of calcium channel blockers is also associated with lower total and cardiovascular-specific mortality in HD patients. Minoxidil is a very potent vasodilator that is generally reserved for dialysis patients with severe hypertension. Hypertensive dialysis patients who are noncompliant with their medications may benefit from transdermal clonidine therapy once a week. The majority of dialysis patients need a combination of several antihypertensive drugs for adequate BP control.     

A shift in the Th(1)/Th(2) ratio accompanies the clinical remission of systemic lupus erythematosus in patients with end-stage renal disease.

BACKGROUND: Patients suffering from systemic lupus erythematosus (SLE) with renal involvement often show remission of systemic clinical activity after progression to end-stage renal disease (ESRD). SLE is characterized by predominantly humoral, T-helper (Th)(2)-mediated autoimmune responses. Since ESRD induces a state of immunodeficiency that affects the balance of Th cell subsets, we hypothesized that a Th(1) shift induced by ESRD leads to clinical remission of SLE. METHODS: Using single-cell measurement of intracellular cytokines by flow cytometry after polyclonal stimulation with PMA/ionomycin, helper cell profiles were analysed in SLE patients with preserved renal function and in SLE patients with ESRD, from both isolated peripheral blood mononuclear cells (PBMC) and whole blood. RESULTS: Using the whole-blood assay, patients with SLE and preserved renal function showed a predominance of Th(2) cells compared to healthy controls (patients, Th(1)/Th(2) ratio 6.0+/-1.0 vs controls, 9.0+/-1.0; P<0.05). In contrast, SLE patients with ESRD have significantly more Th(1) cells (36.8+/-5.0%) than those without ESRD (23.4+/-3.6%; P<0.05). This results in an enhancement of the Th(1)/Th(2) ratio to 12.1+/-2.6, which is not significantly different from healthy controls. These data were confirmed using a PBMC-based assay. CONCLUSIONS: SLE patients with preserved renal function show a bias in the differentiation of Th cells towards Th(2). Once ESRD occurs, the Th(1)/Th(2) ratio normalizes. This may contribute to the remission of Th(2)-mediated autoimmune diseases such as SLE.     

The importance of diabetic nephropathy in current nephrological practice.

BACKGROUND: Diabetic nephropathy has become the major cause of end-stage renal disease (ESRD) in the western world and is forecast to become the most frequent cause of ESRD in the African continent and in developing countries in other areas. METHODS: A discussion to achieve a consensus on key points relating to diabetic nephropathy. RESULTS: Given the catastrophic consequences of diabetes not only for renal function but also for the cardiovascular system, major efforts should be aimed at prevention. The cornerstone of primary prevention (development of microalbuminuria) is a tight control of blood pressure and blood glucose. Although ACE inhibitors have proved effective in preventing the development of microalbuminuria in normotensive patients, this is not the case, in comparison with other classes of antihypertensive drugs, in those who are hypertensive but normoalbuminuric. Secondary prevention (transition to overt nephropathy) and tertiary prevention (progression of established nephropathy to ESRD) benefit from the use of inhibitors of the renin-angiotensin system, whilst the role of tight glycaemic control is more controversial at these stages. Therapeutic lifestyle changes are also important. They should include body weight control combined with regular physical exercise, cessation of smoking and reduced salt intake. The pathogenesis of diabetic nephropathy and its association with hypertension, accelerating renal damage, is complex. It involves genetic factors, altered renal sodium handling with sodium retention, metabolic disturbances and oxidative stress with the formation of advanced-glycation end products (AGEs) and reactive oxygen species. CONCLUSIONS: Although the awareness of the importance of normalizing blood pressure levels and tight glycaemic control have allowed improved survival of diabetic patients, the mortality excess remains unacceptably high in patients with diabetic nephropathy. New treatment strategies are under investigation, including inhibitors of AGE formation, protein kinase C inhibitors, antioxidants, glycosaminoglycans, PPAR-gamma agonists and COX-2 inhibitors.     

ACE-inhibitor use and the long-term risk of renal failure in diabetes

The incidence of end-stage renal disease (ESRD) owing to diabetes has continued to increase despite the extensive use of angiotensin-converting enzyme (ACE) inhibitors to prevent diabetic nephropathy, primarily from evidence of short-term effectiveness. We assessed the long-term effect of ACE inhibitors on the risk of ESRD. We formed a population-based cohort of all diabetic patients treated with antihypertensive drugs in the Province of Saskatchewan, Canada, between 1982 and 1986. The patients were followed up to the end of 1997 to identify cases of end-stage renal failure. A nested case-control analysis was used with the controls matched to each case on age, diabetes type, and duration of follow-up. The cohort comprised 6102 subjects, of which the 102 cases who developed end-stage renal failure were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of end-stage renal failure associated with the use of ACE inhibitors was 2.5 (95% confidence interval 1.3-4.7), whereas it was 0.8 (95% confidence interval 0.5-1.4) for beta-blockers and 0.7 (95% confidence interval 0.4-1.3) for calcium antagonists. The rate ratio of end-stage renal failure with the use of ACE inhibitors was 0.8 (95% confidence interval 0.3-2.5) during the first 3 years of follow-up, but increased to 4.2 (95% confidence interval 2.0-9.0) after 3 years. ACE-inhibitor use does not appear to decrease the long-term risk of end-stage renal failure in diabetes. Our data suggest instead that ACE inhibitors might actually increase this risk, which may possibly contribute to the continued increasing incidence of ESRD owing to diabetes.     

Is there an epidemic of HIV Infection in the US ESRD program?

Surveys revealed increases in the prevalence of HIV-infected patients in the US end-stage renal disease (ESRD) program in the 1980s and early 1990s, with clustering in young black men 25 to 44 yr old. Since the availability of highly active antiretroviral therapy in 1996, the prognosis of HIV-infected patients has improved, and therapy has been shown to change the course of classic HIV-associated nephropathy. We used the United States Renal Data System database to determine if the incidence and prevalence of HIV-infected patients with renal disease has increased in the ESRD program, by means of principal diagnoses and comorbid AIDS-defining diagnoses.As the number of US patients living with AIDS increased 57% from 214,711 in 1995 to 337,017 in 2000, and the number of incident ESRD patients increased 29.9% from 72,827 to 94,602, the number of incident HIV-infected patients increased only by 3.5%, from 1133 to 1171. Over this time, the percentage of incident ESRD patients with HIV infection fell from 1.56% to 1.24%. Among black men 25 to 44 yr of age, HIV infection as a proportion of incident ESRD cases fell from 8.5% to 6.2% from 1995 to 2000. The incident rate per million of AIDS or HIV infection in black men aged 25 to 44 fell from 107 in 1995 to 78 per million in 2000. The incidence rate for HIV-infected women in the ESRD program rose 14% while it declined 7% in men. Almost 2000 HIV-infected women, or 28.8% of the population, have initiated therapy for ESRD with hemodialysis. The number of prevalent cases increased in absolute numbers 81.3% from 2687 to 4871 (0.90% to 1.16% of the ESRD program). One-year survival rates for HIV-infected incident ESRD patients increased from 53.1% to 67.1% from 1995 to 2000.Although these values may be underestimates because of underreporting due to confidentiality concerns and lack of biopsy confirmation, we conclude that although the prevalence of HIV infection is increasing in the US ESRD population, the increase as a proportion of the program is minimal and is due to better survival after development of renal failure. The incidence of HIV infection in the US ESRD program is stable. Highly active antiretroviral therapy may be responsible for the change in epidemiology of HIV infection in the US ESRD program.     

Maps of end-stage renal disease and amounts of angiotensin-converting enzyme inhibitors prescribed in Japan

BACKGROUND: We recently found regional differences in the incidence of end-stage renal disease (ESRD) in Japan, which is generally ethnically homogeneous, suggesting that factors other than genetic may contribute to the difference. Here, we examined regional differences in the amounts of expenses spent on antihypertensives, especially angiotensin-converting enzyme (ACE) inhibitors, in our search for an explanation. METHODS: Annually, the Japanese Society for Dialysis Therapy reports the numbers of patients entering maintenance dialysis in each prefecture of Japan since 1982. We used the findings for 1995 to 2000 to calculate the annual incidence of ESRD in each of the 11 regions of Japan. In addition, regional differences in annual amounts paid for antihypertensive drugs, presumably corresponding to the amounts used, during the same 6 years, corrected for population, were estimated. RESULTS: As in our 1982 to 1998 study, the incidence of ESRD was high in Okinawa, Kyushu, and Shikoku, while low in Hokuriku, Koshinetsu, and Tohoku (P < 0.0001) [one-way repeated measures analysis of variance (ANOVA)]. We found regional differences in the corrected sum paid for total antihypertensive drugs, ACE inhibitors and calcium antagonists. Only ACE inhibitors were negatively correlated with the incidence of ESRD by linear and multiple regression analyses. CONCLUSION: The renal protective effects of ACE inhibitors have been established by results with animal models of progressive nephropathy and large-scale clinical trials. Our epidemiologic results for Japan as a whole show the same protective effects still more convincingly from a different approach.     

End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.

BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.     

Underuse of American College of Cardiology/American Heart Association Guidelines in hemodialysis patients

Patients with end-stage renal disease (ESRD) are at high risk for cardiovascular disease (CVD) and therefore should be treated according to ACC/AHA Guidelines. Scant data are available concerning the actual use of cardioprotective drugs in this population. The use of angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, aspirin, and statins was assessed in 271 (72% males, 66% Caucasians) high-risk ESRD patients on hemodialysis. The study population comprised 27% smokers, 95% with hypertension, 38% with diabetes, and 44% with dyslipidemia; 44% of patients had overt CVD at baseline, including 9% with heart failure, 9% with prior myocardial infarction, and 3% with previous myocardial revascularization. One-third of all patients were not receiving any cardioprotective drugs; among those patients who were, 42% were on one drug, 21% were on two, 3.7% were on three, and 1.5% were on four. The most prescribed agent was ACE-I (35.8%), followed by aspirin (30.6%), and beta-blockers (28.0%). The use of statins was remarkably and significantly low (4.1%) (p < 0.001), even in the higher risk subgroups (patients with diabetes or macrovascular disease). ACE-I plus aspirin was the most prescribed combination (8.5%). Cardioprotective agents recommended for risk-factor modification by the ACC/AHA Guidelines for their well-established efficacy in the general population were underutilized in this cohort of high-risk hypertensive hemodialysis patients, despite an elevated prevalence of clinically evident CVD. Speculatively, this fact may be relevant to better understand the known increased cardiovascular morbidity-mortality associated with chronic renal disease.     

Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease.

BACKGROUND: Hypertension contributes to the progression to renal failure. A genetic susceptibility to hypertension may predispose to the development of end-stage renal disease (ESRD) and promote a more rapid progression to ESRD in patients with renal diseases. Genes encoding for angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and aldosterone synthase (CYP11B2) are candidates for abnormal blood pressure regulation. METHODS: Genotyping was performed in 327 control subjects and 260 ESRD patients for the M235T-AGT, the insertion/deletion (I/D)-ACE, and the -344T/C-CYP11B2 gene polymorphisms using polymerase chain reaction, gel analysis, and appropriate restriction digest when required. RESULTS: Genotype frequencies did not differ significantly between ESRD patients and controls. When ESRD diabetic subjects were compared with diabetic patients without nephropathy, the prevalence of the AGT-MM genotype was lower (28.1 vs. 52.8%, P < 0.01), while the AGT-TT genotype was higher (15.6 vs. 2.7%, P < 0.05). The AGT-TT genotype was associated with a faster progression to ESRD in patients with glomerulonephritis (P < 0.05). In the total ESRD population, progression of renal disease was faster with the ACE-DD than with the DI and II alleles (P < 0.05). This association was particularly strong when the interaction with the AGT genotype was analyzed, with a rapid progression in ACE-DD as compared with ACE-DI and II in patients with the AGT-MM genotype (P < 0.01). CONCLUSIONS: Susceptibility for ESRD and faster progression to ESRD are linked with the AGT genotype in diabetic patients. Faster progression to ESRD is associated with the ACE genotype when the total population with ESRD and with the AGT genotype when patients with glomerulonephritis are considered. Thus, genes of the renin-angiotensin-aldosterone system are candidate genes for further understanding of the interindividual differences in the development and course of ESRD.     

Kidney Transplantation in HIV-Positive Patients: Report of Our First 7 Cases

Introduction

Infection with human immunodeficiency virus (HIV) is associated with end-stage renal disease (ESRD). Although many teams initially were reluctant to offer kidney transplantation as a therapeutic option in HIV-positive patients with ESRD, new drug regimens introduced in the late 1990s have dramatically improved the life expectancy in these patients.

Objective

To report the results of the first 7 kidney transplantation procedures in HIV-positive patients at our institution.

Patients and Methods

Patients were selected to minimize the risks of HIV disease progression, opportunistic infections, and tumors. Protease-inhibitor therapies were suspended because of possible interaction with immunosuppression drugs. The induction regimen did not include lymphocyte-depleting drugs. After undergoing transplantation, patients were monitored by the transplantation and infectious disease teams.

Results

To date, all patients are alive with functioning grafts. We did not observe any episodes of acute rejection, and there were few adverse events. Drug tolerance was good for both immunosuppression and antiretroviral therapies.

Conclusion

Kidney transplantation in HIV-positive patients with ESRD is warranted. Provided that patients are carefully selected, good results can be achieved with few adverse events, episodes of acute rejection, and drug interactions. Posttransplantation, these patients must be closely monitored by both the transplantation and infectious diseases teams to ensure optimal management.     

DPP-4抑制剂治疗合并中重度肾功能不全2型糖尿病的有效性及安全性Meta分析

目的 二肽基肽酶-4抑制剂[Dipeptidyl peptidase-4(DPP-4)inhibitors]是近几年逐渐被接受并运用于2型糖尿病合并肾功能不全患者的一种新型降糖药,然而其安全性及耐受性仍需要进一步验证.因此我们通过Meta分析评价DPP-4抑制剂对于伴有肾损害的2型糖尿病患者的临床疗效及安全性,为临床治疗选择提供参考数据.方法 计算机检索PubMed、EMBASE、Elsevier Science、Cochrane图书馆等数据库文献,检索时间从建库至2015年7月,关键词为“2型糖尿病”和“DPP-4抑制剂”(分别包括西格列汀sitagliptin,沙格列汀saxagliptin,维格列汀vildagliptin,里格列汀linagliptin和特力利汀Teneligliptin)和“糖尿病肾病”或“糖尿病肾脏疾病”或“慢性肾功能不全”.通过摘要或全文阅读筛选观察DPP-4抑制剂与安慰剂或其他降糖药进行疗效及安全性对照观察的RCT研究以及队列研究相关文献纳入Meta分析.结果 纳入12项研究(13篇文献),共2838例患者;Meta分析结果显示,总体比较DPP-4抑制剂组能够有效地降低糖化血红蛋白(HbAlC)水平(权重均数差weighted mean difference,WMD-0.57,95％ CI[-0.54,-0.38],P＜0.00001),但异质性较大(I2=93％);亚组分析提示对比安慰剂组,DPP-4抑制剂对HbA1C的效应更加明显,且异质性较低(WMD-0.62,95％ CI[-0.71,-0.53],P＜0.00001,I2=4％);肾功能损害分层的亚组分析显示在中度与重度肾功能损害亚组中,DPP-4抑制剂均能显著降低HbA1C水平(中度组WMD-0.19,95％ CI [-0.38,-0.01],P=0.04,I2=90％,重度组WMD-0.56,95％CI[-0.66,-0.46],P＜0.00001,I2=86％).而DPP-4抑制剂对于快速血糖(Fasting Plasma Glucose,FPG)水平则无明显影响(总体效应),对比安慰剂也未显示有统计学差异(WMD 0.03,95％ CI[-0.33,0.39],P=0.86,I2=90％).而在安全性评价中,与安慰剂组比DPP-4抑制剂组低血糖的风险稍高(OR[95％CI]:1.38[1.07,1.78],P=0.01,I2=0％),而与其他降糖药组相比DPP-4抑制剂组低血糖风险则显著下降(OR[95％CI]:0.46 [0.33,0.65],P＜0.0001,I2=31％).肾功能分层分析提示,无论是中度肾损害组还是重度肾功能不全组中DPP-4抑制剂组低血糖风险与对照组均无统计学差异(中度OR[95％CI]:1.34 [0.89,2.04],P=0.16,I2=37％,重度OR[95％ CI]:1.04,[0.74,1.48],P=0.81,I2=0％).不良事件总体分析未显示DPP-4与对照组间有统计学差异(OR[95％CI]:0.93 (0.79,1.13),P=0.81,I2=0％),且肾功能亚组分析亦无明显差异:中度肾功能不全(OR[95％ CI]:0.80 [0.52,1.21],P=0.29,I2=0％),重度肾功能不全(OR[95％CI]:0.99 [0.65,1.50],P=0.95,I2=0％);药物相关不良事件与死亡风险DPP-4抑制剂组与对照组间无统计学差异,药物相关不良事件(OR[95％ CI]:0.93[0.71,1.22],P=0.6,I2=7％;死亡OR[95％CI]:0.77 [0.47,1.26],P=0.3,I2=0％).结论 对于中度至重度肾功能不全(包括终末期肾衰竭及透析)的2型糖尿病患者,DPP-4抑制剂仍是一个安全有效的降糖药,但由于受文献资料数量及质量限制,仍需要大样本、多中心、设计良好的RCT进一步验证.     

HIV-positive renal recipients can achieve survival rates similar to those of HIV-negative patients

BACKGROUND: Although patients positive for HIV were once thought to be unsuitable candidates for kidney transplantation, their increasing numbers with end-stage renal disease (ESRD) and the introduction of highly active antiretroviral therapy has indicated that they should no longer be excluded for transplantation. To counteract suggestions that human immunodeficiency virus (HIV) patients received suboptimal kidneys, we provide studies of kidneys transplanted from the same donor into patients with and without HIV. METHODS: United Network for Organ Sharing kidney transplant data between 1997 and 2004 were analyzed. Graft and patient survival of 38 HIV patients who had received a renal transplant were compared with the survival of 38 recipients who had received a graft from the same donor. RESULTS: The 38 HIV-positive recipients were younger (49.0 vs. 52.3 years, P=0.14) and had lower peak panel-reactive antibodies (PRA; 5.1% vs. 15.6%, P=0.07) when compared with their bilateral donor to HIV-negative recipients. Sirolimus was used more frequently in HIV patients than in non-HIV patients (36.8% vs. 23.7%, P=0.09). The serum creatinine at 1, 3, and 5 years posttransplantation were higher in HIV patients when compared to non-HIV patients. Although not statistically significant, graft survival was higher among HIV-positive patients compared with their negative controls (76.1% vs. 65.1% at 5 years, P=0.21), as was patient survival (91.3% vs. 87.3% at 5 years, P=0.72). More grafts failed due to death with a functioning graft than rejection in HIV-positive patients. CONCLUSION: This study supports the position that there is no longer an ethical question surrounding the use of kidneys for HIV-positive patients.     

APOL1 risk variants predict histopathology and progression to ESRD in HIV-related kidney disease

With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.