Expert opinion on pharmacotherapy of kidney disease in HIV-infected patients

Introduction: Human immunodeficiency virus (HIV) infection is associated with the development of a wide spectrum of kidney diseases. HIV-associated nephropathy (HIVAN) is the most common cause of chronic kidney disease (CKD) in HIV-infected individuals and predominantly affects patients of African ancestry. HIVAN is a leading cause of end-stage renal disease (ESRD) among African–Americans.

Areas covered: An overview of the spectrum of kidney disease in patients with HIV is given. Current pharmacologic interventions to treat kidney disease in HIV are discussed. This review will enhance knowledge regarding the most common causes of kidney disease in HIV-infected patients. An understanding of the principles related to pharmacotherapy in HIV-infected patients with kidney disease will also be gained.

Expert opinion: Kidney disease is an important cause of morbidity and mortality in HIV-infected patients. The most common cause of chronic kidney disease in this population is HIV-associated nephropathy, which is caused by viral infection of the renal epithelium. Several medications that are commonly used in HIV-infected patients can have adverse effects on the kidneys and the doses of many antiretroviral medications need to be adjusted in patients with impaired renal function.     

筛查某家族性局灶节段硬化性肾小球肾炎家庭的NPHS2基因

目的 为某个有两个儿童患者死于局灶节段硬化性肾小球肾炎的家庭查找致病原因.方法 取孕18周后的羊水进行染色体检查,同时提取夫妇静脉血DNA、死亡男童肾组织DNA及胎儿羊水DNA,进行NPHS2基因检测.结果 胎儿染色体未见异常;孕妇NPHS2基因检测发现c.954C＞T变异,此改变位于第8外显子,不引起氨基酸的改变,为...     

MAGI-2 orchestrates the localization of backbone proteins in the slit diaphragm of podocytes

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Endogenous asymmetrical dimethylarginine and hypertension associated with puromycin nephrosis in the rat

1. The present experiments were designed to investigate the role of asymmetrical N^G,N^G-dimethyl-L-arginine (ADMA) in causing hypertension associated with the focal and segmental glomerulosclerosis (FSGS) produced by a single bolus of puromycin aminonucleoside (PAN) and successive injection of protamine for 7 days in rats which had undergone unilateral nephrectomy.
2. After the unilateral nephrectomy, and administering PAN and protamine, histological examinations of the kidney revealed a typical FSGS, that is, evident abnormalities including segmental mesangial proliferation, obliteration of glomerular capillary lumens and adhesions between the glomerulus and Bowman''s capsule could be observed. Changes in the glomerular epithelial cells consisted of the swelling with bleb formation.
3. In the FSGS rats, urine volume and urinary protein were significantly (P<0.05 and P<0.005) increased throughout 4-week experimental period, while the creatinine clearance was significantly (P<0.005) and transiently decreased, and recovered 4 weeks later. These changes were associated with the sustained elevation of the systolic blood pressure.
4. ADMA levels in aortic endothelial cells, plasma and urine were significantly (P<0.05 and P<0.005) increased in the FSGS rats, but the level in the kidney remained unchanged.
5. The basal level and net production of cyclic GMP in the aortic vessel wall with endothelium when stimulated by norepinephrine and acetylcholine were significantly (P<0.05 and P<0.01) attenuated in the FSGS rats.
6. There were significant and positive correlations between systolic blood pressure (y) and ADMA levels (x) in endothelial cells (y=4.43x+122.2, r=0.979, P<0.0001), plasma (y=0.10x+71.9, r=0.921, P<0.001) and urine (y=0.48x+126.9, r=0.699, P<0.005), but not significant in the kidney (y=0.06x+102.7, r=0.252, NS).
7. These findings suggest that ADMA as an endogenous inhibitor of NO synthesis may play an important role for the pathogenesis in the hypertension associated with the experimental FSGS in the rat.

     

Ofatumumab in post‐transplantation recurrence of focal segmental glomerulosclerosis in a child

FSGS is a potentially devastating form of nephrotic syndrome. Treatment of SRNS can be difficult, especially post‐transplantation. The current therapy of post‐transplant SRNS includes plasmapheresis, ACE‐I, CNI, and monoclonal antibodies (rituximab). Patients who are refractory to these interventions have limited therapeutic alternatives. We present a case of a patient with SRNS secondary to FSGS. He did not respond to immunosuppressive medications prior to transplant, progressed to ESRD, and was started on chronic hemodialysis. He received a DDKT which was complicated by post‐transplant FSGS recurrence. A course of plasmapheresis, rituximab, and CNI were administered with some response. Ofatumumab was then given to the patient. As a result, the patient achieved partial remission. Ofatumumab may be a safe and effective option for post‐transplant recurrence of FSGS.     

Early recurrent nephrotic syndrome after renal transplantation in children with focal segmental glomerulosclerosis.

BACKGROUND: We analysed risk factors to predict the recurrence of nephrotic syndrome and the therapeutic efficacy of plasmapheresis combined with oral cyclophosphamide (PE+CPM) in early recurrent nephrotic syndrome after transplantation in children with focal segmental glomerulosclerosis (FSGS). METHODS: Medical records after 1990 of 16 children with biopsy-proven idiopathic FSGS and renal transplantation before the age of 18 years were reviewed. RESULTS: Early recurrence of nephrotic syndrome developed in six cases (37. 5%). While early kidney graft biopsies, performed within the first week after the onset of recurrence, revealed diffuse effacement of foot process only, late biopsies contained segmentally sclerosed glomeruli as well. Among several possible risk factors, the mean duration from onset of original nephrotic syndrome to development of end-stage renal disease was shorter in the recurrent group (P=0.045) and the percentage of globally sclerosed glomeruli was higher in the non-recurrent group (P=0.001). PE+CPM therapy resulted in complete remission of nephrotic syndrome if it was started early and if there was no evidence of accompanying acute rejection. CONCLUSION: These results support more liberal use of living-related donors for renal transplantation of children with FSGS and ESRD, considering the shortage of cadaveric donors in our society and relatively good efficacy of the early and intensive PE+CPM therapy for early recurrent nephrotic syndrome.     

Pre-transplant Screening for Non-HLA Antibodies: Who should be Tested?

Retrospective studies of angiotensin II type 1 receptor antibodies (AT1R-Ab) and anti-endothelial cell antibodies (AECA) have linked these antibodies to allograft injury. Because rising healthcare costs dictate judicious use of laboratory testing, we sought to define characteristics of kidney transplant recipients who may benefit from screening for non-HLA antibodies. Kidney recipients transplanted between 2011 and 2016 at Johns Hopkins, were evaluated for AT1R-Ab and AECA. Pre-transplant antibody levels were compared to clinical and biopsy indications of graft dysfunction. Biopsies were graded using the Banff' 2009–2013 criteria. AT1R-Ab and AECA were detected using ELISA and endothelial cell crossmatches, respectively. AT1R-Ab levels were higher in patients who were positive for AECAs. Re-transplanted patients (p?<?0.0001), males (p?=?0.008) and those with FSGS (p?=?0.04) and younger (p?=?0.04) at time of transplantation were more likely to be positive for AT1R-Ab prior to transplantation. Recipients who were positive for AT1R-Ab prior to transplantation had increases in serum creatinine within 3?months post-transplantation (p?<?0.0001) and developed abnormal biopsies earlier than did AT1R-Ab negative patients (126?days versus 368?days respectively; p?=?0.02). Defining a clinical protocol to identify and preemptively treat patients at risk for acute rejection with detectable non-HLA antibodies is an important objective for the transplant community.     

De novo CMV‐associated collapsing focal segmental glomerulosclerosis in a kidney transplant recipient

Collapsing focal segmental glomerulosclerosis (FSGS) is a variant of FSGS and is associated with severe nephrotic syndrome and acute kidney injury and can occur after kidney transplantation. The exact mechanism of collapsing FSGS after kidney transplantation is unknown, but potential causes include autoimmune diseases, certain malignancies, bisphosphonates, m‐TOR inhibitors, interferon‐alpha, HIV infection, and other viruses. We describe a case of de novo Cytomegalovirus (CMV)‐associated collapsing FSGS in a kidney transplant recipient with a UL97 phosphotransferase mutation that was successfully treated with intravenous ganciclovir, intravenous immunoglobulin, and steroids.