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Everolimus-Associated Thrombotic Microangiopathy Following Renal Transplant: A Case Report

Leong ZCW, Kong JHL, Khor SY, Liew YF

Cureus, 2024 Oct;16(10):e71535.
PMID: 39544564 DOI: 10.7759/cureus.71535

Thrombotic microangiopathy (TMA) is a serious complication that may affect post-renal transplant recipients. De novo TMA has been linked to the use of transplant immunosuppressive agents, including calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORi). We report a case of a 41-year-old female renal transplant recipient who presented with hemolytic anemia, thrombocytopenia, and acute allograft dysfunction. Before her presentation, she was on immunosuppression with oral tacrolimus, oral prednisolone, and oral everolimus. Her renal biopsy showed features of TMA, which led to extensive workup to identify the underlying cause. Eventually, everolimus was recognized as the cause of secondary TMA as her hemolytic parameters and renal allograft function recovered following discontinuation of this drug. This case report highlights the association of everolimus with TMA in a post-renal transplant patient. Early recognition and drug withdrawal can prevent allograft loss.
A prospective study of incidence and outcome of acute kidney injury among hospitalised patients in Malaysia (My-AKI)

Goh CY, Visvanathan R, Leong CT, Hooi LS, Ch'ng CC, Yee SY, et al.

Med J Malaysia, 2023 Nov;78(6):733-742.
PMID: 38031214

INTRODUCTION: The incidence of acute kidney injury (AKI) among hospitalised patients has not been well studied in Malaysia.
MATERIALS AND METHODS: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included.
RESULTS: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17).
CONCLUSION: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.
Calcific Uremic Arteriolopathy (CUA) Among Malaysian Dialysis Patients: Clinical Characteristics, Treatment, and Outcomes

Lee YW, Tan MH, Bavanandan S, Bee BC, Lim CTS, Mohd R, et al.

Cureus, 2024 Nov;16(11):e73711.
PMID: 39677159 DOI: 10.7759/cureus.73711

Background Calcific uremic arteriolopathy (CUA) is a rare but debilitating disease affecting patients with kidney disease. Reported risk factors of CUA in the literature include female sex, obesity, diabetes mellitus, and vitamin K antagonists' (VKAs) usage. CUA prevalence in Malaysia is unknown and has not been reported before. Methods A multicenter observational study was conducted in 13 centers all over Malaysia to study the clinical characteristics, treatment, and outcomes of CUA. The data of patients confirmed with CUA between January 1, 2016, and December 31, 2021, was collected from medical records by each center's nephrologists. Results Out of 33 confirmed CUA cases, 69.7% were females, and 66.7% were Malay with a mean age of 47.33 ± 13.80 years old. The mean BMI was 25.66 ± 9.77 kg/m2, and 18.2% were classified as obese (BMI > 30). Two-thirds of the patients were on hemodialysis (HD), and the mean dialysis vintage was 6.2 ± 4.11 years. A majority (87.9%) have hypertension, 33.3% are diabetic, and 27.3% have coronary artery disease. Only 15.2% of the patients were on warfarin at the time of diagnosis. A total of 78.8% of patients were taking calcium-based phosphate binders during diagnosis. Investigation results showed calcium, 2.44 ± 0.29 mmol/L; phosphate, 2.18 ± 0.67 mmol/L; CaXPO4 = 5.41 ± 1.90; and parathyroid hormone, 181.14 ± 153.23 pmol/L. About half (54.5%) had skin biopsy confirmation done. Distribution of lesions was 57.6% peripheral and 30.3% central. For treatment of CUA, there were 57.6% usage of non-calcium-based phosphate binders, 48.5% cinacalcet, 30.3% sodium thiosulphate, and 33.3% had parathyroidectomy. Half (54.5%) of our CUA patients died within three months from diagnosis. The mean time from diagnosis to mortality was 4.12 ± 5.59 months. A majority (45.5%) died from septicemia caused by infections. Interestingly, there were a few rare presentations of CUA such as pulmonary calciphylaxis, heart and lung calcifications, liver and spleen calcifications, and genital lesions. One patient had resistant CUA and was given a trial of lipid apheresis for 10 sessions. Conclusion This is the first and largest multicenter study looking into the characteristics, treatment, and outcome of CUA in Malaysia. Majority of patients in Malaysia undergo HD as kidney replacement therapy; hence, our results correlate with this. The incidence of CUA was estimated to be 6.6 per 10,000 dialysis patients in this study and the mortality rate is very high. This is consistent with worldwide data which reported mortality as high as 60%.
Clinical effectiveness of a Malaysian-manufactured CAPD product: A randomised trial

Mak WY, Leong CT, Ong LM, Bavanandan S, Mushahar L, Goh BL, et al.

Perit Dial Int, 2021 05;41(3):273-283.
PMID: 33733911 DOI: 10.1177/0896860821993954

BACKGROUND: We compared the clinical effectiveness of a new peritoneal dialysis (PD) product with polyvinyl chloride-containing tubing (Stay Safe Link®, SSL) with the plastic-free alternative (Stay Safe®, STS) in patients on continuous ambulatory peritoneal dialysis (CAPD).
METHOD: A multicentre, parallel, randomised, controlled, open-label, non-inferiority trial was conducted. Adult patients receiving CAPD were randomised in a 1:1 ratio to SSL or STS. The primary outcome was the rate of peritonitis after 1 year of follow-up.
RESULTS: A total of 472 subjects were randomised (SSL, n = 233; STS, n = 239). One subject in each group was excluded from the analysis as they withdrew consent before the first dialysis dose. Four hundred and seventy subjects (SSL, n = 232; STS, n = 238) were included in the modified intention-to-treat analysis. Non-inferiority between two groups was established as no significant difference was found in peritonitis rate (incident rate ratio: 0.91, 95% CI: 0.65-1.28). No significant difference was detected in weekly Kt/V (p = 0.58) and creatinine clearance (p = 0.55). However, the average ultrafiltration volume was significantly lower in SSL, with a mean difference of 93 ml (p < 0.01). SSL also demonstrated a 2.57-times higher risk of device defect than STS (95% CI: 1.77-3.75).
CONCLUSION: SSL was non-inferior in peritonitis rate compared to plastic-free STS over 1 year in patients requiring CAPD. There was no difference in the delivered dialysis dose, but there was a higher rate of device defects with SSL.