Kidney transplantation from an HIV‐positive cadaveric donor

Kidney transplantation is the gold‐standard therapy for select HIV‐positive patients with ESRD. Since the Italian Ministry of Health defined the guidelines for organ donation from HIV‐positive persons in 2018, we report the first case of renal transplantation from an HIV‐positive cadaveric donor in two HIV‐positive recipients in Italy. The donor was a 50‐year‐old male, deceased due to post‐anoxic encephalopathy, with a history of HIV infection in HAART, undetectable viral load, and HCV‐related chronic hepatitis that had been previously treated. The first recipient was a 59‐year‐old female with a prior history of drug addiction, and she suffered from ESRD secondary to HIV nephropathy. The patient followed preoperative HAART with a good viral response and undetectable HIV viral load. She also had a history of HCV‐related chronic hepatitis that had been successfully treated. The right kidney was uneventfully transplanted. The patient developed an asymptomatic reinfection of endogenous BK virus. The second recipient was a 41‐year‐old male with ESRD secondary to polycystic kidney disease. The patient was HIV‐positive in HAART, with a good viro‐immunologic response and an undetectable HIV viral load. He suffered from a severe form of hemophilia A and HCV‐related chronic hepatitis, which had been previously treated with undetectable HCV RNA. The left kidney was uneventfully transplanted. At the end of follow‐up, both patients had a healthy condition with stable renal function, a persistently good viral response and undetectable HIV and HCV viral loads. These encouraging preliminary results seem to confirm the safety and effectiveness of kidney transplantation from select HIV‐positive donors.     

Belatacept conversion in an HIV‐positive kidney transplant recipient following anti‐thymocyte globulin induction

Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus (HIV)‐positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti‐thymocyte globulin (ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor‐specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction.     

In sickness and in health: Living HIV positive kidney donation from a wife to her husband,with 7 years' post‐transplant follow‐up

Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for kidney transplantation. After the introduction of ART, several studies have demonstrated comparable patient and graft outcomes between HIV‐negative and HIV‐positive kidney recipients. The US Congress passed the HIV Organ Policy Equity (HOPE) Act in 2013, which permits research in the area of HIV‐positive to HIV‐positive transplantation. HIV‐infected living donation is also permitted under the HOPE Act. However, there is a concern regarding the safety of kidney donation in an HIV‐infected person, given the risk of renal disease associated with HIV infection. We report here the case of successful kidney transplantation from HIV‐positive living donor to HIV‐positive recipient performed in our center on July 2012. To the best of our knowledge, this is the earliest case done in this medical context to be reported in the literature, therefore, potentially carrying several important messages to the transplantation community. In the present case, the living‐donor kidney transplant was performed between a married couple infected with same strain of HIV‐1, both on effective ART with efficiently suppressed viral replication and satisfactory pre‐transplantation immune status.     

HIV-assoziierte Nierenerkrankungen

The human immunodeficiency virus (HIV) epidemic is still ongoing and HIV-associated kidney diseases are a heterogeneous group of renal injuries. Glomerular and tubular damage can occur in patients infected with HIV and can be caused directly due to infection of renal cells or indirectly by the immune response and side effects of antiretroviral therapy. The pathogenesis is not well understood and makes a specific therapy difficult. The most frequent kidney disease in HIV-positive individuals is HIV-associated nephropathy (HIVAN), which mostly affects patients of African descent. Furthermore, HIV-associated thrombotic microangiopathy (HIV-TMA) and immune complex-mediated kidney disease (HIVICK) can also occur. As a result of combined antiretroviral therapy the life expectation of HIV patients is increased as well as comorbid kidney diseases. Treatment of terminal renal failure in HIV positive patients involves dialysis or transplantation, which requires careful adjustment of the dosage and consideration of the side effects of the antiretroviral regimen.     

Heart failure in subjects with chronic kidney disease: Best management practices

Renal dysfunction is common in patients with heart failure (HF) and can complicate HF therapy. Treating patients with HF and kidney disease is difficult and requires careful assessment, monitoring and balancing of risk between potential benefits of treatment and adverse impact on renal function. In this review, we address the pathophysiological contexts and management options in this adversarial relation between the heart and the kidney, which exists in a substantial proportion of HF patients. Angiotensin converting enzyme inhibitors and β-blockers are associated with similar reductions in mortality in patients with and without renal insufficiency but usually are less often prescribed in patients with renal insufficiency. Careful monitoring of side effects and renal function should be done in all patients with renal insufficiency and prompt measures should be adopted to prevent further complications.     

The use of cell cycle arrest biomarkers in the early detection of acute kidney injury. Is this the new renal troponin?

Acute kidney injury (AKI) has a high prevalence in critical care patients. Early detection might prevent patients from developing chronic kidney disease and requirement for renal replacement therapy. If we compare AKI with acute coronary syndrome, in which an increase in cardiac troponin may trigger early diagnosis and therapeutic intervention, we could extrapolate a similar technique in patients with early AKI without changes in urinary frequency or serum creatinine. The objective is to identify biomarker-positive, creatinine-negative patients that would allow therapeutic interventions to be initiated before finding changes in serum creatinine, preventing kidney damage. Tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 are cell cycle arrest biomarkers that have demonstrated, in recent clinical trials, to have good sensitivity and specificity for early detection of AKI. Other recent studies have shown that the joint use of these biomarkers with serum creatinine and urine production could improve the prognosis of AKI in critical patients. The application of these biomarkers in clinical practice would enable the early identification of patients at risk of AKI, establishing interventions that would improve the survival of renal function.     

Rapid communication: acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity

Drug-induced renal failure is a relatively common event in patients infected with HIV. This group of patients receives a number of potentially nephrotoxic medications for a variety of illnesses. The acyclic nucleoside phosphonates cidofovir and adefovir are antivirals that possess significant nephrotoxicity. Interestingly, tenofovir disoproxil fumurate (DF) is structurally similar to these 2 agents, yet seems to be less nephrotoxic based on a few published studies in HIV patients with intact renal function. We present a case in which acute renal failure developed after therapy with tenofovir DF in a patient with HIV and stable chronic kidney disease.     

Renal disease among males with haemophilia

Haematuria is common among persons with haemophilia (PWH), but its long-term effects on the kidney and renal function are not well defined. In addition, infection with human immunodeficiency virus (HIV) or hepatitis C, or exposure to nephrotoxic agents as therapy for these infections may place PWH at increased risk for renal disease. To examine factors associated with chronic renal disease (CRD) and acute renal disease (ARD) in PWH, we analysed data collected from the medical records of 3422 males with haemophilia living in six US states from 1993 to 1998. Renal disease cases were ascertained from among 2075 persons who were hospitalized at least once over the 6-year period. Of these, 60 (2.9%) were diagnosed during one or more hospitalizations with either ARD (29/60) or CRD (31/60). In multivariate analyses, we examined associations between renal disease and demographic and clinical factors including age, race, haemophilia type and severity, hypertension, diabetes, history of recent renal bleeds, presence of an inhibitor, and infection with hepatitis C or HIV. HIV infection and hypertension were strongly associated with both ARD and CRD. PWH who had ARD were also more likely to have an inhibitor than those without this diagnosis. PWH who had CRD were more likely to be older and non-white and to have had a recent admission for a kidney bleed than those without diagnosed CRD. In summary, we found that HIV infection and haemophilia-related factors including inhibitors and kidney bleeds were associated with renal disease in a cohort of males with haemophilia.     

A national review of assessment and monitoring of HIV-infected patients

Objectives

The British HIV Association (BHIVA) audit subcommittee aimed to survey UK clinic policy and practice regarding baseline assessment and immunization of newly diagnosed HIV‐positive patients, and frequency of follow‐up and testing in established patients in the UK.

Methods

UK centres providing HIV care were requested to complete an online survey between October 2006 and March 2007.

Results

111 centres participated in the survey. 89.2% of centres routinely performed baseline HIV resistance testing. 99% of centres had a policy of routine screening for hepatitis B. Only 91% of centres were routinely offering a sexual health screen at diagnosis. Frequency of routine follow‐up for patients not requiring antiretroviral therapy (ART) and stable on ART varied between three and six months.

Discussion

This review showed variations in practice regarding the post diagnosis assessment and routine monitoring of HIV patients. It is of concern that not all centres perform baseline HIV resistance testing. It has also been noted that hepatitis B vaccination is not being offered to non‐immune patients at diagnosis. Less frequent follw‐up of stable patients (both on and off ART) should allow resources to be focussed on those with specific clinical needs.     

Spectrum of chronic kidney disease in HIV-infected patients

Objectives

The aim of the study was to investigate the prevalence and aetiology of chronic kidney disease (CKD) and trends in estimated glomerular filtration rate (eGFR) in HIV‐infected patients.

Methods

Ascertainment and review of CKD cases among patients attending King's College and Brighton Hospitals, UK were carried out. CKD was defined as eGFR <60 mL/min for ≥3 months. Longitudinal eGFR slopes were produced to examine trends in renal function before, during and after exposure to indinavir (IDV) or tenofovir (TFV).

Results

CKD prevalence was 2.4%. While HIV‐associated nephropathy accounted for 62% of CKD in black patients, 95% of CKD in white/other patients was associated with diabetes mellitus, hypertension, atherosclerosis and/or drug toxicity. Exposure to IDV or TFV was associated with an accelerated decline in renal function (4.6‐fold and 3.7‐fold, respectively) in patients with CKD. In patients initiating IDV, age ≥50 years increased the odds of CKD [odds ratio (OR) 4.9], while in patients initiating TFV, age ≥50 years (OR 5.4) and eGFR 60–75 mL/min (OR 17.2) were associated with developing CKD.

Conclusion

This study highlights the importance of metabolic and vascular disease to the burden of CKD in an ageing HIV‐infected cohort. In patients who developed CKD, treatment with IDV or TFV was associated with an accelerated decline in renal function.     

Hepatitis C virus and kidney: a strong association with different clinical aspects

The most frequent kidney disease associated with chronic hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis in patients with type II mixed cryoglobulinaemia. The principal clinical manifestations of glomerular disease in HCV‐infected patients are the presence of proteinuria and haematuria with or without impaired kidney function. Pharmaceutical regimens vary because the main pathogenesis of renal dysfunction often mediated by cryoglobulins has not been fully elucidated. HCV infection remains common in patients on renal replacement therapy and has an adverse impact on their survival. Safe and effective pharmaceutical regimens have not been yet established and nosocomial spread within dialysis units continues to occur. Monotherapy with interferon for HCV infection is probably more effective in dialysis than in non‐uraemic patients, while experience with ribavirin is limited because of its adverse haemolytic effect. Based on shortage of cadaver kidneys and the fact that HCV renal transplant recipients have better survival than stay on maintenance haemodialysis or at list for transplantation, health organization proposed the use of cadaver kidneys from anti‐HCV‐positive donors, bringing up concerns and conflicting views. This present review describes the main renal manifestations of HCV infection, the epidemiological and clinical characteristics of chronic kidney disease population and comments on the limitations and shortcomings of current therapeutical regiments.     

Renal disease in patients with HIV

As survival continues to improve in the era of highly active antiretroviral therapy, kidney, liver, and cardiac disease have become increasingly important sources of mortality and morbidity in patients with HIV. The incidence of end-stage renal disease in patients with HIV is projected to increase, and the incidence of earlier chronic kidney disease, acute renal failure, and electrolyte abnormalities is likely to be much higher than appreciated. Both acute and chronic kidney disease are more common in the setting of advanced HIV, hepatitis coinfection or liver disease, and medication toxicity. Close collaboration between nephrologists and infectious disease specialists is important to facilitate the identification, diagnosis, and management of acute and chronic kidney disease in patients with HIV. Recently published guidelines highlight the increased awareness of kidney disease in the infectious disease community and provide guidelines for the detection and management of chronic kidney disease in patients with HIV.     

Visit‐to‐Visit Variability of Blood Pressure and Renal Function Decline in Patients With Diabetic Chronic Kidney Disease

The authors previously reported that the visit‐to‐visit variability of blood pressure is correlated with renal function decline in nondiabetic chronic kidney disease. Little is known about the association between visit‐to‐visit variability and renal function decline in patients with diabetic chronic kidney disease. The authors retrospectively studied 69 patients with diabetic chronic kidney disease stage 3a, 3b, or 4. The standard deviation and coefficient of variation of blood pressure in 12 consecutive visits were defined as visit‐to‐visit variability of blood pressure. The median observation period was 32 months. In univariate correlation, the standard deviation and coefficient of variation of blood pressure were not significantly associated with the slope of estimated glomerular filtration rate. There was no significant association between the visit‐to‐visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease, in contrast with our previous study of nondiabetic patients with chronic kidney disease.     

KIDNEY FAILURE STABILIZES AFTER AN INCREASE OVER 2 DECADES

The level of proteinuria is one of the most important predictors for progressive renal function loss in kidney disease. Reduction of urinary protein levels by renin‐angiotensin‐system (RAS) inhibitors limits renal function decline in patients with non‐diabetic and diabetic nephropathies to the point that remission of the disease and regression of renal lesions have been reported. The increasing use of these drugs is possibly at the basis of the stabilization of rates of new cases of kidney failure reported to the US Renal Data System after a 2‐decade period of progressive increases. RAS inhibition, however, may not be effective to the same degree in all patients. For those patients who do not reach a complete remission of proteinuria, treatment procedures to implement renoprotection should include strict blood pressure control (and metabolic control in diabetics), lowering of blood lipids, and lifestyle modifications. Early intervention may be important to maximize renoprotection, especially in diabetics.     

Successful kidney transplantation in a patient with stable multiple myeloma

Renal failure is a common feature of multiple myeloma affecting 20–55% of patients at the initial presentation and is being associated with a significant increase in morbidity and mortality. Renal transplantation for patients with multiple myeloma is rarely considered given the incurable nature of the disease, the risk of post‐transplant disease progression and perceived high risk of infections. Here we report a 57‐year‐old man with end‐stage renal failure attributed to presumed IgA nephropathy, with pre‐existing stable multiple myeloma, who received a kidney transplant from a two haplotype‐matched sibling. Transplantation has been successful and with excellent kidney function and stable multiple myeloma 6 years post‐transplant. This case highlights the potential benefits of renal transplantation in highly selected patients with multiple myeloma.     

Renal artery stenosis and ambulatory blood pressure monitoring: A case report and review of the literature

Renal artery stenosis (RAS) is a prevalent cause of secondary hypertension. Elderly patients with atherosclerosis and young women with fibromuscular dysplasia (FMD) are particularly at risk. Blood pressure screening is often key to this diagnosis, although the reliability of clinical screening has been questioned, and ambulatory blood pressure monitoring (ABPM) likely offers superior ability to diagnose poorly controlled hypertension. In patients with RAS, medical management should be the primary means of therapy; however, in a select group of these patients, renal revascularization may be considered, and has been shown to reduce blood pressure and stabilize chronic kidney disease. In this report, we present a patient diagnosed with RAS due to FMD, found to have significant hypertension via ABPM, and treated successfully with percutaneous renal artery angioplasty; importantly, continuous 24‐hr ambulatory monitoring after pressure gradient guided renal angioplasty confirmed reduction in blood pressure.     

Comparison of glomerular filtration rate estimates vs. 24-h creatinine clearance in HIV-positive patients

Background

Guidelines for kidney function monitoring and antiretroviral drug dosing are available and respectively refer to glomerular filtration rate and creatinine clearance (CrCl).

Objective

The aim of the study was to compare kidney function estimates vs. measured 24‐h CrCl in HIV‐infected subjects.

Methods

A cross‐sectional design was used, with comparison of Cockcroft–Gault (CG), original and simplified modification of diet in renal disease (MDRD) equations vs. measured 24‐h CrCl. Subjects were HIV‐infected, 18–70 years old, without pre‐existing kidney disease.

Results

Results are presented as mean (±standard deviation), unless otherwise stated. The study population consisted of 90 patients, of whom 71% were male, with a mean age of 45 years (±6.5 years). At the time of evaluation, the mean body mass index was 23 (±3.3); mean serum creatinine was 0.91 mg/dL (±0.2 mg/dL); and mean blood urea nitrogen (BUN) was 34.7 mg/dL (±10.6 mg/dL). Differences between paired methods were all significant (P<0.00001), except between CG and simplified MDRD (P=0.21; Pearson r=0.81). In univariate analysis, male gender, CD4 nadir, hepatitis B virus coinfection, BUN and current CD4 cell count showed a significant positive correlation (P<0.2) with the difference between measured 24‐h CrCl and either CG or simplified MDRD estimates. In multivariate analysis, only BUN showed a significant positive correlation (P<0.05).

Conclusions

Estimates were lower than the measurements of 24‐h CrCl. Original MDRD estimates were lower than those with other equations. CG and simplified MDRD estimates showed a satisfactory correlation.     

The effect of foscarnet (phosphonoformate) on human immunodeficiency virus isolation, T-cell subsets and lymphocyte function in AIDS patients

Foscarnet was administered by continuous intravenous infusion in 15 patients with the acquired immunodeficiency syndrome (AIDS) in an open, uncontrolled study. Mean steady state serum concentrations of foscarnet was 261 mumol/l. Treatment was given for 6-21 days, median 14 days, being interrupted prematurely due to renal function impairment in seven patients, and due to other reasons in three patients. Foscarnet therapy was accompanied by improvement of some, probably cytomegalovirus (CMV) related, symptoms but did not otherwise affect the clinical condition of the patients. The occurrence of positive CMV cultures decreased significantly during therapy. Human immunodeficiency virus (HIV) detection by culture was positive in 70-80% of cultures and was unaffected by foscarnet treatment. Eight patients had detectable, free HIV antigen in serum before therapy, and in five of these HIV antigen disappeared during therapy, but reappeared 4-23 weeks after therapy. No patient lost HIV antigen, except during foscarnet therapy. No patient became HIV antigen positive during foscarnet therapy. Immunological parameters did not change during or after foscarnet therapy. Renal function impairment was seen in 9 patients (95% confidence limits, 32-84%), apparently due to reversible tubular damage. At follow-up, serum creatine was normal in all surviving patients. Concomitant medication may have contributed to the renal side-effects. Severe renal function impairment, i.e. serum creatinine above 0.25 mumol/l, was only seen in patients who at the start of foscarnet therapy were chronically affected by their disease. Thus, foscarnet reduces HIV antigen production in AIDS patients. Renal function impairment limits foscarnet use in AIDS patients, but in individuals with less severe manifestations of HIV infection, this side effect may be less frequent.     

Impact of HIV seropositivity on graft and patient survival after cadaveric renal transplantation in the United States in the pre highly active antiretroviral therapy (HAART) era: an historical cohort analysis of the United States Renal Data System

Abstract: Background.National statistics are presented for patient survival and graft survival in patients seropositive for the human immunodeficiency virus (HIV+) at the time of renal transplantation in the era prior to highly active antiretroviral therapy (HAART). Methods. Historical cohort analysis of 63, 210 cadaveric solitary renal transplant recipients with valid HIV serology entries in the United States Renal Data System (USRDS) from 1 January 1987 to 30 June 1997. The medical evidence form was also used for additional variables but, because of fewer available values, was analyzed in a separate model. Outcomes were patient characteristics and survival associated with HIV+ status. Results. Thirty‐two patients (0.05%) in the study period were HIV+ at transplant. HIV+ patients were comparable to the national renal transplant population in terms of gender and ethnic distribution but were younger and had younger donors and better HLA matching than the USRDS population. Patient and graft three‐year survival were significantly reduced in HIV+ recipients (53% graft, 83% patient survival) relative to the USRDS population (73% and 88%, respectively). In multivariate analysis, HIV+ status was independently associated with patient mortality and decreased graft survival in recipients of cadaveric kidney transplants. Conclusions. This analysis was retrospective and may underestimate the number of HIV+ patients transplanted in the United States. Although the clinical details of patient selection for transplant were unknown, these results show HIV+ patients can have successful outcomes after cadaveric renal transplantation, although outcomes are significantly different from HIV– recipients.     

Chronic kidney diseases in long-term survivors after allogeneic hematopoietic stem cell transplantation: monitoring and management guidelines

Chronic kidney disease (CKD) occurs commonly (prevalence of approximately 20% in a large series) after allogeneic hematopoietic stem cell transplantation (HSCT). There are three distinct clinical entities that occur after HSCT: thrombotic microangiopathy (TMA), nephrotic syndrome (NS), and idiopathic or graft-versus-host disease (GVHD)-related CKD. Acute renal function decline occurs in the majority of patients in the first months after transplantation. This acute kidney injury can persist and is a risk factor for the later development of CKD. However, the potentially independent role of GVHD, chronic inflammation, and chronic exposure to calcineurin inhibitors in the development and progression of CKD warrants further investigation. Careful monitoring of blood pressure, renal function, and proteinuria is mandatory in patients undergoing HSCT, especially older patients with pre-existent renal impairment. Renal function should be evaluated before HSCT and monitoring should occur at least every 6 to 12 months in these patients. Renal biopsies are indicated in patients with proteinuria and persistent or progressive rises in serum creatinine to determine etiology and prevent progression to end-stage renal disease (ESRD).