Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.

Association of anemia and mineral and bone disorder with health-related quality of life in Asian pre-dialysis patients.

BACKGROUND: Patients with chronic kidney disease (CKD) have poor health-related quality of life (HRQoL). The association of CKD-related complications such as anemia and mineral and bone disorders (MBD) with HRQoL in pre-dialysis patients is not well-studied. As such, this study aimed to determine the association of anemia and MBD with HRQoL in pre-dialysis patients. METHODS: This was a cross-sectional study involving 311 adult pre-dialysis patients with stage 3-5 CKD from an acute-care hospital in Singapore. Patients' HRQoL were assessed using Kidney Disease Quality of Life Short Form (KDQOL-SF™) and EuroQol 5 Dimensions-3 levels (EQ5D-3L). HRQoL between patients with and without anemia or MBD were compared by separate hierarchical multiple linear regression analyses using various HRQoL scales as dependent variables, adjusted for sociodemographic, clinical and psychosocial variables. RESULTS: After adjusting for MBD, anemia was associated with lower HRQoL scores on work status (WS), physical functioning (PF) and role physical [ß (SE): -10.9 (4.18), p = 0.010; -3.0 (1.28), p = 0.018; and -4.2 (1.40), p = 0.003, respectively]. However, significance was lost after adjustments for sociodemographic variables. Patients with MBD had poorer HRQoL with respect to burden of kidney disease, WS, PF and general health [(ß (SE): -7.9 (3.88), p = 0.042; -9.5 (3.99), p = 0.018; -3.0 (1.22) p = 0.014; -3.6 (1.48), p = 0.015, respectively]. Although these remained significant after adjusting for sociodemographic variables, significance was lost after adjusting for clinical variables, particularly pill burden. This is of clinical importance due to the high pill burden of CKD patients, especially from medications for the management of multiple comorbidities such as cardiovascular and mineral and bone diseases. CONCLUSIONS: Neither anemia nor MBD was associated with HRQoL in our pre-dialysis patients. Instead, higher total daily pill burden was associated with worse HRQoL. Medication reconciliation should therefore be routinely performed by clinicians and pharmacists to reduce total daily pill burden where possible.

Ethnic disparity in prevalence of diabetic kidney disease in an Asian primary healthcare cluster.

AIMS: Diabetic kidney disease (DKD) incidence is rising in Singapore. While measures to prevent onset and early detection of diabetes as well as optimal diabetes and blood pressure control are important, early detection and treatment of DKD at primary care are crucial to ameliorate its course. This study aimed to evaluate the prevalence of DKD in a primary care cluster in Singapore and identify its risk factors in a multi-ethnic Asian population. METHODS: A total of 57,594 patients with type 2 diabetes mellitus (T2DM) followed-up at the National Healthcare Group Polyclinics with estimated glomerular filtration rate and at least two urine albumin/creatinine ratio (UACR) were stratified into DKD stages: normoalbuminuria (UACR <30 mg/g), microalbuminuria (MI, UACR 30-299 mg/g), macroalbuminuria (MA, ≥300 mg/g) and renal impairment (RI, estimated glomerular filtration rate eGFR <60 mL/min per 1.73 m(2)). Factors associated with DKD stages were evaluated. RESULTS: Overall DKD prevalence (T2DM with MI, MA or RI) was high at 52.5%; 32.1% had MI, 5.3% had MA and 15.1% had RI. DKD prevalence within ethnic subpopulations was different: 52.2% of Chinese, 60.4% of Malays and 45.3% of Indians had DKD, respectively. Malays had a 1.42-fold higher DKD prevalence, while Indians had a 0.86-fold lower. Other independent risk factors were age, female gender, duration of diabetes and hypertension, HbA1c and body mass index. CONCLUSION: The high prevalence of DKD and its interethnic differences suggest need for additional measures to optimize the care of T2DM at primary care to mitigate its progression.

Outcomes for kidney transplants at the National University Health System: comparison with overseas transplants.

The 5-year and 10-year graft survivals for 186 deceased donor (DD) transplants performed at National University Health System (NUHS) were 79.9% and 58.4% respectively. 5-year and 10-year patient survivals for DD transplants performed at NUHS were 94.2% and 83.4%. The 5-year and 10-year graft survivals for 128 living donor (LD) transplants performed at NUHS were 90.2% and 72% respectively. 5-year and 10-year patient survivals for DD transplants performed at NUHS were 98.6% and 95.1%. The projected graft half lives were 14.6 and 20.6 years for DD and LD transplants respectively. These results compare favorably with the 10-year survival rates of 40% and 58% for DD and LD grafts reported by the United States Renal Data System (USRDS) in 2010. The younger age and the lower prevalence of diabetes and HLAmismatch in the DD and LD transplant study populations, in comparison to the USRDS population and perhaps better access and compliance to maintenance immunosuppression, could have contributed to these excellent outcomes. The 5-year and 10-year graft survivals for 162 transplants receiving what were likely deceased donor kidneys from China were 89.2% and 69.2% respectively. Although these survivals were apparently better than that for DD performed at NUHS, the advantage for China Tx disappeared when DD with primary non function or vascular thrombosis were excluded from analysis. The 5-year and 10-year patient survivals for 30 transplants receiving live non-related transplants from India were 82.3% and 60.1%. Both groups were considered to have received commercial transplants based on various aspects of history from the patients. Among those receiving China_Tx or India Tx, there were a disproportionate number of males and Chinese; and a significant proportion underwent pre-emptive transplant or transplant after only a short period of dialysis. Prevalence of post-transplant hepatitis B was significantly higher among China_Tx than their DD counterparts (7.7% vs. 1.2%, P = 0.005); likewise, post transplant hepatitis C was significantly higher for India_Tx than their LD counterparts (23.1% vs. 3.4%, P = 0.003). These results suggest that commercialization in transplant, results in inequities to access to transplantation and is associated with compromise in screening for infections among potential donors or in observing safety precautions during dialysis.

Mechanism-based enterohepatic circulation model of mycophenolic acid and its glucuronide metabolite: assessment of impact of cyclosporine dose in Asian renal transplant patients.

Mycophenolic acid (MPA) is mainly metabolized to MPA-glucuronide (MPAG), which may be reconverted to MPA following enterohepatic circulation (EHC). A physiologically realistic EHC model was proposed to estimate and assess the impact of cyclosporine (CsA) dose on the extent of EHC of MPA and MPAG. After the first oral dose of mycophenolate mofetil (MMF), the MPA and MPAG plasma concentration-time data of 14 adult renal transplant patients (12 receiving concomitant CsA and prednisolone and 2 receiving only concomitant prednisolone without CsA) were analyzed by individual pharmacokinetic modeling using a proposed 5-compartment drug and metabolite EHC model with a time-varying gallbladder emptying process. Simulations were performed to assess the influence of the time of bile release after dosing (T(bile)) and the gallbladder emptying interval (tau(gall)) on the EHC process. The extent of EHC for both MPA and MPAG tended to be lower in the group receiving CsA coadministration and decreased with increasing total body weight-adjusted CsA dose. Simulations revealed that T(bile) and tau(gall) influenced the time of occurrence and maximum concentration of the second peak, as well as the extent of EHC, for MPA and MPAG.