Kidney transplantation in people living with human immunodeficiency virus: An overview of the Australian experience.

Kidney transplantation in people living with HIV (PLWHIV) is occurring with increasing frequency. Limited international data suggest comparable patient and graft survival in kidney transplant recipients with and without HIV. All PLWHIV aged ≥18 years who received a kidney transplant between 2000 and 2020 were identified by retrospective data initially extracted from Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), with additional HIV-specific clinical data extracted from linked local health-care records. Twenty-five PLWHIV and kidney failure received their first kidney transplant in Australia between January 2000 and December 2020. Majority were male (85%), with median age 54 years (interquartile range, IQR 43-57). Focal segmental glomerulosclerosis was the most common primary kidney disease (20%), followed by polycystic kidney disease (16%). 80% of patients underwent induction with basiliximab and none with anti-thymocyte globulin (ATG). Participants were followed for median time of 3.5 years (IQR 2.0-6.5). Acute rejection occurred in 24% of patients. Two patients lost their allografts and three died. Virological escape occurred in 28% of patients, with a maximum viral load of 190 copies/mL. In conclusion, kidney transplantation in PLWHIV in Australia is occurring with increasing frequency. Acute rejection is more common than in Australia's general transplant population, but this does not appear to be associated with higher rates of graft failure or mortality out to four years.

Human immunodeficiency virus and solid organ transplantation: a 15-year retrospective audit at a tertiary Australian transplant centre.

BACKGROUND: The incidence of end-stage organ disease in people living with human immunodeficiency virus (HIV) (PLWH) is increasing, as people live longer due to potent, tolerable antiretroviral therapy (ART). Consequently, the number of PLWH who would benefit from solid organ transplant (SOT) is rising. The SOT experience in PLWH in Australia remains limited. Aim To retrospectively review the outcomes for SOT in PLWH at our service, in Victoria, Australia. METHODS: A retrospective cohort study of PLWH undergoing SOT over a 15-year period was performed. Adult PLWH age >18 years were eligible and identified from the Victorian HIV Service database. Descriptive statistics were used to summarise baseline demographics and clinical data, and outcomes following SOT. RESULTS: Nine virologically suppressed PLWH underwent SOT from HIV-negative donors (five kidneys, two livers and two bilateral sequential lung transplants). All patients were male, with a median age of 57.3 years (interquartile range (IQR) = 54.3-60.1) and CD4 count of 485 (IQR = 342-835) at transplantation, and comorbidities were common at baseline. After a median follow up of 3.9 years (IQR = 2.7-7.6), 8 (89%) patents were alive, 7 (78%) had functioning grafts, although 5 (56%) experienced organ rejection. Infections were common. Two patients required modification to their ART due to significant drug-drug interactions prior to transplant, while 5 (56%) had modifications post-SOT. No patients experienced HIV virologic failure. CONCLUSION: PLWH with end-stage organ disease experience good clinical and functional outcomes and should be considered for SOT where indicated. However, multidisciplinary planning and care is essential to optimise care in this patient group.

Safety and utility of kidney biopsy in patients with estimated glomerular filtration rate < 30 ml/min/1.73 m2.

AIM: Kidney biopsy (KBx) is the gold standard for evaluation of kidney disease, but is associated with a higher risk of complications in patients with reduced glomerular filtration rate (GFR). We studied the safety and utility of KBx in patients with eGFR <30 ml/min/1.73 m2 . METHODS: Consecutive adult patients with eGFR <30 ml/min/1.73 m2 , who were planned for a KBx and consented to participate were prospectively enrolled. Patients with solitary/transplant kidney or acute kidney injury were excluded. Haemoglobin was checked on the day of KBx and repeated 18-24 h later along with a screening ultrasound. Post-KBx complications were noted and their risk-factors analysed. The utility of the KBx was graded as effecting significant, some, or no change to subsequent management. RESULTS: Of the 126 patients included, 75% were male, 27.7% were diabetic, and the median eGFR was 13.5 ml/min/1.73m2 . Major complications occurred in 5.6%. Peri-renal haematomas were detected in 37.3%, and haematomas ≥2 cm were significantly more frequent in those with eGFR <15 ml/min/1.73 m2 (29.2% vs. 13%, p = .032). Dialysis was a risk factor, while pre KBx blood transfusion, diabetes and higher serum albumin were protective against any complication. KBx was more likely to make a significant difference in management in those with eGFR 15-29 ml/min/1.73m2 (44.1% vs. 11.1%, p < .001). Increasing age, lower serum creatinine and albumin were independently associated with KBx utility. CONCLUSION: KBx is relatively safe in severe kidney disease but its risk to benefit balance needs to be carefully considered when eGFR is <15 ml/min/1.73m2 .

Treatment of invasive IMP-4 Enterobacter cloacae infection in transplant recipients using ceftazidime/avibactam with aztreonam: A case series and literature review.

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo-ß-lactamase (MBL)-producing Gram-negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer ß-lactamase inhibitors such as avibactam have well-established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL-producing organisms. Conversely, aztreonam has activity against MBL-producing organisms but is often inactivated by other co-existing ß-lactamases. Here, we report four cases of invasive MBL-CPE infections in transplant recipients caused by IMP-4-producing Enterobacter cloacae who were successfully treated with a new, mechanism-driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high-risk patients with CPE infection, with reduced drug interactions and toxicity.

Developing nephrology services in low income countries: a case of Tanzania.

BACKGROUND: The burden of kidney diseases is reported to be higher in lower- and middle-income countries as compared to developed countries, and countries in sub-Saharan Africa are reported to be most affected. Health systems in most sub-Sahara African countries have limited capacity in the form of trained and skilled health care providers, diagnostic support, equipment and policies to provide nephrology services. Several initiatives have been implemented to support establishment of these services. METHODS: This is a situation analysis to examine the nephrology services in Tanzania. It was conducted by interviewing key personnel in institutions providing nephrology services aiming at describing available services and international collaborators supporting nephrology services. RESULTS: Tanzania is a low-income country in Sub-Saharan Africa with a population of more than 55 million that has seen remarkable improvement in the provision of nephrology services and these include increase in the number of nephrologists to 14 in 2018 from one in 2006, increase in number of dialysis units from one unit (0.03 unit per million) before 2007 to 28 units (0.5 units per million) in 2018 and improved diagnostic services with introduction of nephropathology services. Government of Tanzania has been providing kidney transplantation services by funding referral of donor and recipients abroad and has now introduced local transplantation services in two hospitals. There have been strong international collaborators who have supported nephrology services and establishment of nephrology training in Tanzania. CONCLUSION: Tanzania has seen remarkable achievement in provision of nephrology services and provides an interesting model to be used in supporting nephrology services in low income countries.

Spectrum of biopsy proven renal disease in South Asian children: Two decades at a tropical tertiary care centre.

AIM: We report findings from a large single centre paediatric renal biopsy cohort in South Asia. METHODS: We analyzed all renal biopsies performed on children aged ≤18 years between 1996 and 2015 at our centre. The clinical characteristics and histological diagnosis pertaining to each case, distribution of renal diseases in children with various clinical presentations, and changes in the pattern of kidney disease during the study period were analyzed. RESULTS: A total of 1740 paediatric kidney biopsies were performed during the study period. The mean age was 12.8 ± 4.9 years (8 months to 18 years) and the male: female ratio was 1.5:1. The most common indication for renal biopsy was nephrotic syndrome (63.2%) followed by acute nephritic syndrome (13%). Minimal change disease was the most common cause of nephrotic syndrome while endocapillary proliferative glomerulonephritis (65.7% infection related), remained the commonest cause of acute nephritic syndrome. IgA nephropathy was the commonest cause of chronic kidney disease. Contrary to trends in European paediatric cohorts, the frequency of lupus nephritis increased over the two decades of the study, while that of endocapillary proliferative glomerulonephritis did not show any appreciable decline. CONCLUSION: This study provides the largest data on biopsy proven renal disease in children from South Asia published till date and highlights important differences in the spectrum and trends of kidney disease compared to data from other regions.

Immunohistochemical Glomerular Expression of Phospholipase A2 Receptor in Primary and Secondary Membranous Nephropathy: A Retrospective Study in an Indian Cohort with Clinicopathological Correlations.

BACKGROUND: Limited published literature exists on the utility and standardization of anti-phospholipase A2 receptor (anti-PLA2R) immunohistochemistry (IHC) for the diagnosis of primary membranous nephropathy (MN). The study aimed to validate anti-PLA2R IHC for the diagnosis of primary MN and clinicopathological correlations in an Indian cohort. METHODS: Subjects included patients with primary and secondary MN diagnosed between January 2012 and August 2014 with an adequate renal biopsy and at least 1 year of clinical follow-up. Anti-PLA2R IHC was performed in all cases with miscellaneous renal lesions as controls. Electron microscopy was performed in selected cases. Sensitivity and specificity of anti-PLA2R IHC to identify primary MN was evaluated. Histopathological analyses of primary and secondary MN were done with clinicopathological correlations including serum creatinine, eGFR, chronic kidney disease stage, 24-h urine protein, serum cholesterol, serum albumin, and hypertension at presentation and follow-up, using the Kruskal-Wallis test and Spearman rank correlation. A p value of ≤0.05 was considered statistically significant. RESULTS: In 153 MN patients (99 primary, 54 secondary) and 37 miscellaneous controls, anti-PLA2R IHC differentiated primary from secondary MN with a sensitivity of 70.2% and a specificity of 96.6%. Secondary MN had increased mesangial matrix expansion compared to primary MN (p = 0.001). Severe nephrotic syndrome, impaired renal function, and hypertension were all more common in primary than in secondary MN. CONCLUSION: Anti-PLA2R IHC is a specific marker to distinguish primary MN from secondary MN.

Interactions between thyroid disorders and kidney disease.

There are several interactions between thyroid and kidney functions in each other organ's disease states. Thyroid hormones affect renal development and physiology. Thyroid hormones have pre-renal and intrinsic renal effects by which they increase the renal blood flow and the glomerular filtration rate (GFR). Hypothyroidism is associated with reduced GFR and hyperthyroidism results in increased GFR as well as increased renin - angiotensin - aldosterone activation. Chronic kidney disease (CKD) is characterized by a low T3 syndrome which is now considered a part of an atypical nonthyroidal illness. CKD patients also have increased incidence of primary hypothyroidism and subclinical hypothyroidism. The physiological benefits of a hypothyroid state in CKD, and the risk of CKD progression with hyperthyroidism emphasize on a conservative approach in the treatment of thyroid hormone abnormalities in CKD. Thyroid dysfunction is also associated with glomerulonephritis often by a common autoimmune etiology. Several drugs could affect both thyroid and kidney functions. There are few described interactions between thyroid and renal malignancies. A detailed knowledge of all these interactions is important for both the nephrologists and endocrinologists for optimal management of the patient.

Leflunomide with low-dose everolimus for treatment of Kaposi's sarcoma in a renal allograft recipient.

Current treatment of Kaposi's sarcoma is reduction of immunosuppression with or without addition of mammalian target of rapamycin inhibitors (mTORi). Akt signalling plays a central role in oncogenesis of Kaposi's sarcoma. We describe a case of multifocal Kaposi's sarcoma in a renal allograft recipient, which showed unsatisfactory early response to immunosuppression reduction along with everolimus therapy but completely resolved after adding leflunomide. mTORi impair Kaposi's sarcoma oncogenesis by inhibiting mTOR downstream from the Akt signalling. Leflunomide inhibits Akt phosphorylation. This synergistic effect may be beneficial in treatment of Kaposi sarcoma and needs to be explored in trials.

Disseminated cysticercosis.

Cysticercosis is a common public health problem in the Tropics. However, disseminated cysticercosis is rare. We report a patient with chronic liver disease and seizures, in whom a simple plain radiographic examination helped in narrowing down the differential diagnosis to disseminated cysticercosis. The diagnosis was confirmed by serum cysticercal antibody enzyme-linked immunosorbent assay (ELISA) and computerized tomography of the brain.