Vertebrate extracellular fluids lie below the threshold for spontaneous calcium phosphate (Ca–Pi) precipitation; yet, they remain supersaturated enough to foster crystal growth if unchecked. Calciprotein particles (CPP) and their smaller precursor calciprotein monomers (CPM) have emerged as fast-acting “mineral buffers” that mitigate abrupt local oversaturation. Although these complexes typically contain only trace amounts of Ca–Pi relative to total plasma levels, they exhibit remarkably high turnover kinetics, with clearance from the circulation within minutes, far outpacing hormonal loops that operate on timescales of hours to days. By forming ephemeral colloidal assemblies, CPM/CPP help maintain fluid-phase stability and avert uncontrolled crystallization “accidents” in microenvironments such as the intestine or bone-remodeling sites. However, under chronic mineral stress, such as in chronic kidney disease, multiple inhibitory factors (e.g., fetuin-A, pyrophosphate) can become deficient, enabling persistent generation of more advanced, crystalline CPP species. These “modified” CPP can adsorb additional ligands (e.g., apolipoproteins, microbial remnants, growth factors) and have been linked to inflammatory and pro-calcific changes in vascular and immune cells. Despite their minor quantitative contribution, these rapidly mobilized colloids may exert outsized influence on vascular and skeletal homeostasis, underscoring the need to clarify their origins, biological roles, and potential therapeutic targeting in disorders of mineral metabolism.

Background Mineral metabolism abnormalities are an almost universal feature of CKD and are believed to contribute to the development of many adverse events. Calciprotein particles (CPP) form spontaneously in biological fluids from calcium and phosphate together with the glycoprotein fetuin-A. While CPP formation is a part of normal mineral homeostasis, levels are chronically elevated in CKD. Several assays have been developed to measure serum CPP, each linking high CPP levels to adverse clinical outcomes in CKD. However, direct comparisons among these assays are lacking. The aim of this exploratory study was to compare these assays to assess their association with CKD progression and mortality. Methods We measured baseline CPP levels using various methods on stored serum samples from 189 participants in a prospective observational cohort study of patients with CKD stage 3/4. Three assays were used to measure CPP: (1) ELISA (fetuin-A CPP), (2) low-density CPP (L-CPP) and high-density CPP by gel filtration, and (3) primary CPP and secondary CPP (CPP-II) by flow cytometry. We examined the association of each CPP measure with all-cause mortality and CKD progression using unadjusted and covariate-adjusted Cox proportional hazard regression models. Results In fully adjusted models, high-density CPP (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.05 to 2.23; P = 0.028) and CPP-II (HR, 3.11; 95% CI, 1.97 to 4.98; P < 0.001) were significantly associated with an increased risk of all-cause mortality. In addition, L-CPP (HR, 1.91; 95% CI, 1.43 to 2.62; P < 0.001), primary CPP (HR, 1.31; 95% CI, 1.04 to 1.65; P = 0.023), and CPP-II (HR, 1.66; 95% CI, 1.20 to 2.29; P = 0.002) were significantly associated with CKD progression. Conclusions In a cohort of patients with CKD stages 3 and 4, serum CPP-II levels demonstrated the strongest association with all-cause mortality, while L-CPP levels showed the strongest association with CKD progression.

Background:Chronic kidney disease (CKD) is a global concern that presents significant challenges for disease management. Several factors drive CKD prevalence, including primary risk factors, such as type 2 diabetes and hypertension, and an ageing population. Inside CKD is an international initiative that aims to raise awareness of the substantial burden incurred by CKD. Methods:Using a peer-reviewed microsimulation method, the clinical burden of CKD was estimated from 2022 to 2027. Demographic data from the Americas, Europe, and Asia-Pacific/Middle East were used to generate virtual populations and to project the prevalence of CKD, kidney replacement therapy, associated cardiovascular complications, comorbid conditions, and all-cause mortality in the CKD population over the modelled time frame. Findings:Across the 31 participating countries/regions, the total prevalence of CKD was projected to rise to 436.6 million cases by 2027 (an increase of 5.8% from 2022), with most cases (∼80%) undiagnosed. Inside CKD projected a mean of 8859 cases of heart failure, 10,244 of myocardial infarction, and 7797 of stroke per 100,000 patients with CKD by 2027. Interpretation:The clinical impact of CKD is substantial and likely to increase; the high prevalence of undiagnosed cases and associated complications may benefit from the implementation of health policy interventions that promote screening, earlier diagnosis, and interventions to improve outcomes. Funding:AstraZeneca.

AIM:We aimed to better understand the prevalence of chronic kidney disease in Abu Dhabi, UAE, where a very diverse ethnic population lives, each with their own risk profile. METHODS:Data were analysed on all patients who were tested for serum creatinine in December 2019 for 4 years within our healthcare network. We analysed data for kidney disease by age, gender and nationality to study differences in prevalence and risk. RESULTS:The entire cohort (EC) consisted 1 925 672 samples from 703 122 patients. 24% of patients had GFR < 90 mL/min/1.73 m2 (CKD2-5), 4% had more severe kidney dysfunction (CKD3-5) and 2% had UACR >3 mg/mmol and with GFR > 90 (CKD1). The long follow-up (LFU) group comprised 45.6% of patients who had eGFR on at least two occasions more than 90 days apart, and of these 19.5% had sustained eGFR <90, and 5.2% had CKD3-5. Males had lower eGFR than females in the EC (RR 1.68) and the LFU group (RR 1.76). Emirati Females had the lowest prevalence in the EC (2.9%) and expatriate females in the LFU (3.5%) groups. The relative risks of CKD in expatriate males were highest in the EC (2.14) and the LFU (2.39) groups. When we looked at the age distribution by nationality there were highly significant differences in some populations being highly represented at younger ages. CONCLUSION:The prevalence of kidney disease in Abu Dhabi has a male predominance, with younger expatriates highly represented. A targeted strategy to identify those at high risk may identify early CKD to prevent progression to end-stage kidney disease.

Abstract Background and Aims Chronic Kidney Disease (CKD) affects approximately one in ten people around the world and is associated with an increased risk of adverse cardiorenal outcomes and mortality. In low- and middle-income countries (LMICs), the situation is aggravated by the paucity of kidney replacement therapies (KRTs). The objective of this study was to review the literature around CKD prevalence to understand the future epidemiology and economic burden of CKD in four LMICs from different continents. Method Inside CKD is a project designed to perform a microsimulation on a representative patient cohort to simulate renal disease progression into the future, and to model the effects of interventions based on population and disease characteristics. A pragmatic literature review was performed to obtain the inputs required to adapt the Inside CKD model to project the epidemiological and economic burden of CKD in four World Bank (2022) classified LMICs (Bolivia, Kenya, Sri Lanka and Uzbekistan). Using a data quality scoring system designed for the Inside CKD programme, a model input template was created to guide the country-specific literature search, to identify country demographics, epidemiological data including CKD staging data, renal registries, comorbidities (type 2 diabetes and hypertension), complications data (stroke, myocardial infarction, heart failure) and economic data including health costs and quality-of-life measures. Additional needs, challenges or country specific risk factors have also been identified. Results Literature reviews identified the best sources of demographic, epidemiological data as well as the main drivers of CKD in the four countries (e.g. hypertension, type 2 diabetes, heart failure). In addition, the reviews identified the best proxy data to use when country-specific data was not available. The UN World Prospects database was selected to derive the current and future population dynamics in the four countries. For Kenya, data from local sources, sub-Saharan African and Uganda were utilised to estimate the primary drivers of CKD: a 2018 meta-analysis reported a CKD prevalence of 18% in sub-Saharan Africa and was used to derive the eGFR and UACR data required to project CKD prevalence. CKD prevalence by stage was also identified for Bolivia. A large-scale study across 12 countries with consistent methodology estimated a CKD prevalence of around 5.5% in Bolivia. CKD data from Kazakhstan was selected as a proxy for Uzbekistan, which had a low prevalence of 1.3%. Country-specific challenges were also identified: in Kenya, results showed the importance of malnutrition, infection and climate as key drivers of CKD. In Sri Lanka and Uzbekistan, environmental factors (air and water pollution) and agricultural activity may contribute to high CKD prevalence in rural areas alongside more common risk factors such as hypertension. In Sri Lanka, CKD has been estimated at around 8.2% in the general population versus 15.0% in areas where groundwater is consumed. For Bolivia, additional parameters including occupation, altitude, seasonal weather variation and extreme temperatures may exacerbate CKD risk. Conclusion CKD is a major public health problem in LMICs but with diverse drivers. Local capacities and healthcare financing priorities vary between regions and depend upon competing demands of acute conditions, infections and non-communicable diseases. Forecasting future CKD burden is helpful for policy and planning purposes. There is a clear need to tailor policies beyond early screening and proactive management to tackle country-specific challenges such as occupation, infection, seasonal weather variation and genetics.

Introduction: The lifesaving practice of organ donation and transplantation has been deeply impacted by the COVID-19 pandemic. Up until January 2022, donors were screened out of the donor pool in the UAE if they tested positive for SARS-COV-2. Methods: We report a case of a COVID-19 infected donor whose organs were transplanted to 3 uninfected recipients (2 kidneys, 1 liver). A national guideline was created to permit a change in practice after the engagement and endorsement of relevant stakeholders. Recipients were informed of Donor’s COVID status and consented. Results: The Donor was a 35-year-old previously healthy male who was hospitalized due to a spontaneous intracerebral bleed of unclear etiology and met brain death criteria. SARS-COV-2 PCR testing was obtained on admission and remained persistently positive beyond day 14 of admission. The donor was otherwise afebrile and had normal inflammatory markers with no evidence of an infectious pulmonary process on CT scan. The donor did not receive any COVID therapies. The donor had received 3 doses of the Sinopharm vaccine, the last dose being 3 months prior to admission. Organ retrieval occurred on day 24 of COVID-19 PCR positivity to three uninfected recipients in two different transplant centers in the UAE. Conclusion: Transplanting solid organs from non-lung COVID positive donors can effectively maintain an expanded donor pool during the pandemic.

Aim: To establish and quantify the time saved by redirecting nursing workload from recording and entering haemodynamic data during chronic dialysis sessions by linking dialysis machines directly to the electronic medical record. Methods: We developed a bespoke interface from the HL7 feed from the dialysis machines (largely Fresenius 5008) to our EMR system (Cerner). We quantified the time nurses spent with the patient, computer, dialysis machine and sorting our patient related issues by observation using independent observers in a time and motion study. We performed these observations before and after implementation of the computer interface. We established patient and nursing acceptance by survey. We established adequacy of observations by counting the number of patients who received the minimum number of observations recorded in the system before and after implementation. Results: Implementation of a dialysis machine direct EMR interface reduced the time the nurses spent with the computer significantly by similar to 9 % (around 28 min, p < 0.05) per dialysis shift, and this was accompanied by a similar increase in time spent sorting out patient-related issues. The interface was well accepted by staff and patients. An immediate benefit was a similar to 60 % improvement in the adequacy of recording vital signs in our dialysis patients. Then simply by showing these results to the nursing staff there was further improvement. Conclusions: In these days of machine interconnectivity there is really no good reason why dialysis nurses should be used to transfer data between machines. It is far better to utilise their skills in helping patients with their medical issues. We have shown that such a link improves efficiency, patient and staff satisfaction and dialysis governance.

ABSTRACT Background Calciprotein particles (CPP) are colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of cardiovascular disease in chronic kidney disease (CKD). Emerging evidence suggests non-calcium-containing phosphate binders may reduce serum CPP in patients with kidney failure who require dialysis; however, it is unclear whether similar interventions are effective in patients with earlier stages of CKD. Methods The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) was a multi-centre, placebo-controlled, randomized trial of lanthanum carbonate on cardiovascular markers in 278 participants with stage 3b/4 CKD. In this pre-specified exploratory analysis, primary (CPP-I) and secondary CPP (CPP-II) were measured in a sub-cohort of participants over 96 weeks. Treatment groups were compared using linear mixed-effects models and the relationship between serum CPP and pulse wave velocity (PWV) and abdominal aortic calcification (AAC) was examined. Results A total of 253 participants had CPP data for baseline and at least one follow-up timepoint and were included in this analysis. The mean age was 62.4 ± 12.6 years, 32.0% were female and the mean estimated glomerular filtration rate (eGFR) was 26.6 ± 8.3 mL/min/1.73 m2. Baseline median serum CPP-I was 14.9 × 104 particles/mL [interquartile range (IQR) 4.6–49.3] and median CPP-II was 3.3 × 103 particles/mL (IQR 1.4–5.4). There was no significant difference between treatment groups at 96 weeks in CPP-I [22.8% (95% confidence interval −39.2, 36.4), P = 0.65] or CPP-II [−18.3% (95% confidence interval −40.0, 11.2), P = 0.20] compared with a placebo. Serum CPP were not correlated with baseline PWV or AAC, or with the progression of either marker. Conclusions Lanthanum carbonate was not associated with a reduction of CPP at 96 weeks when compared with a placebo in a CKD cohort.

Introduction: Elevated levels of fibroblast growth factor-23 (FGF23) in chronic kidney disease (CKD) are associated with progression of CKD. FGF23 inhibits proximal tubular phosphate reabsorption, raising phosphate concentrations in the tubular fluid of functioning nephrons, predisposing to spontaneous precipitation of calcium phosphate crystals and resultant tubular injury. Calciprotein monomers (CPM) form spontaneously in biological fluids when clusters of calcium phosphate ions are bound by the liver-derived glycoprotein fetuin-A. Serum CPM are elevated in CKD and are postulated to trigger FGF23 secretion. CPM are also readily filtered at the glomerulus into the tubular fluid, suggesting that higher CPM levels could be associated with progression of CKD via FGF23-mediated increased phosphate load but also through direct effects in the proximal tubule. Methods: ACADEMIC was a prospective observational study of 200 stable outpatients with CKD stages 3 and 4. Participants were followed until commencement of dialysis or death. In this study, we examined a sub-cohort of 189 participants who had baseline serum available for measurement of CPM. Cox proportionate hazard regression models were used to examine the association between CPM and a composite kidney disease outcome (commencement of dialysis or reduction in estimated glomerular filtration rate [eGFR] >30%). Linear regression models were used to examine the association between CPM and annualized eGFR slope. Results: Relative to the lowest tertile, the highest tertile of CPM was associated with increased risk of the composite kidney disease outcome in univariate models and after sequential adjustment for conventional risk factors for progression of CKD (adjusted hazard ratio 4.22; 95% confidence interval [CI] 1.91, 9.33, p < 0.001). Natural log-transformed CPM was also inversely associated with eGFR slope in univariate and multivariate adjusted models (adjusted β-coefficient −1.66, 95% CI: −3.10, −0.22, p = 0.024). In exploratory mediation analysis, the association between serum CPM and eGFR slope was partially mediated by iFGF23; however, the majority of the association was direct and independent of the iFGF23 pathway. Conclusion: Elevated levels of CPM are associated with the progression of CKD. This association was partially mediated via FGF23, consistent with recent evidence that FGF23 predisposes to spontaneous precipitation of calcium phosphate crystals leading to tubular injury. However, serum CPM also appeared to have a direct association with eGFR slope, raising the possibility that CPM may also be associated with progression of CKD through additional pathways.

ABSTRACT Background Calciprotein particles (CPPs), colloidal mineral-protein nanoparticles, have emerged as potential mediators of phosphate toxicity in dialysis patients, with putative links to vascular calcification, endothelial dysfunction and inflammation. We hypothesized that phosphate binder therapy with sucroferric oxyhydroxide (SO) would reduce endogenous CPP levels and attenuate pro-calcific and pro-inflammatory effects of patient serum towards human vascular cells in vitro. Methods This secondary analysis of a randomised controlled crossover study compared the effect of 2-week phosphate binder washout with high-dose (2000 mg/day) and low-dose (250 mg/day) SO therapy in 28 haemodialysis patients on serum CPP levels, inflammatory cytokine/chemokine arrays and human aortic smooth muscle cell (HASMC) and coronary artery endothelial cell (HCAEC) bioassays. Results In our cohort (75% male, 62 ± 12 years) high-dose SO reduced primary (amorphous) and secondary (crystalline) CPP levels {−62% [95% confidence interval (CI) −76 to −44], P < .0001 and −38% [−62 to −0.14], P < .001, respectively} compared with washout. Nine of 14 plasma cytokines/chemokines significantly decreased with high-dose SO, with consistent reductions in interleukin-6 (IL-6) and IL-8. Exposure of HASMC and HCAEC cultures to serum of SO-treated patients reduced calcification and markers of activation (IL-6, IL-8 and vascular cell adhesion protein 1) compared with washout. Serum-induced HASMC calcification and HCAEC activation was ameliorated by removal of the CPP-containing fraction from patient sera. Effects of CPP removal were confirmed in an independent cohort of chronic kidney disease patients. Conclusions High-dose SO reduced endogenous CPP formation in dialysis patients and yielded serum with attenuated pro-calcific and inflammatory effects in vitro.

Calcium and phosphate levels in serum are maintained well below the point of spontaneous precipitation yet well above the solubility of bulk bone mineral, readily sustaining crystal growth and ripening once seeded. Despite this metastability, unwanted mineral deposition outside osseous tissue is typically only observed in old age and in certain disease states (e.g., chronic kidney disease). For decades, hyperphosphatemia has been considered a prime driver of ectopic mineralization in chronic kidney disease, yet many other mammalian species have much higher serum phosphate concentrations than human adults without obvious sequelae.

Hemodialysis patients are at high risk of hospitalization. Predicting such risk in dialysis patients may be critical to maintaining quality of life and reducing costs to the healthcare system. In this paper, we present and fractional polynomial stepwise logistic regression model to specify how routinely collected blood test variables could be linked to a significant increase in hospitalization risk. We found that eight of nineteen variables were significantly able to predict hospitalization risk; albumin (p<0.05), creatinine (p<0.05), calcium (p<0.01), bicarbonate (p<0.01), hemoglobin (p<0.05), mean cell hemoglobin concentration (MCHC) (p<0.0001), mean corpuscular volume (MCV) (p<0.0001), and potassium (p<0.01). The model achieved accuracy, sensitivity, and specificity of 77.31%, 83.03%, and 69.05%, respectively.

Chronic kidney disease-associated pruritus (CKD-aP) is a common condition amongst patients with advanced chronic kidney disease (CKD). Several studies have confirmed that more than four out of ten early-stage CKD patients suffer from this condition, while its prevalence among CKD patients on dialysis reaches up to seven out of ten. It is noted to be associated with other disabling symptoms and serious outcomes. It has significant impact on sleep, mood, daily activities, and quality of life of CKD patients, and increased mortality risk of patients on hemodialysis. The Dialysis Outcomes and Practice Patterns Study found 17% higher mortality among patients with moderate to extreme pruritus compared with patients with no or mild pruritus. Despite its high prevalence, ill-effect, and suffering associated with it, CKD-aP remains surprisingly under-reported on the patient's part and under -recognized by the healthcare team. Even upon being noticed, it remains unattended and poorly treated. Its etiopathogenesis is complex and not fully understood. Many treatment options are available but good quality evidence about most of those is absent, and to date, only two medications are approved for use in this condition. While a validated guideline is very much required for the benefit of the patients and caretakers, further research on several aspects of this issue is required.

Some epidemiological data have implicated blood groups in susceptibility to coronavirus disease 2019 (COVID-19) infection. We were interested to see if there was any apparent effect of different ABO blood groups on susceptibility to COVID-19 infection in unvaccinated hemodialysis (HD) patients, as they had a high rate of mortality from this infection. Blood group O has been suggested to be protective against COVID-19 infection; however, since the ABO frequency is affected by ethnicity, we looked at infection frequency and blood group and corrected the expected frequency for the ethnicity of our cohort. We examined 249 HD patients presenting with a positive COVID-19 polymerase chain reaction regarding their ABO blood group and compared the ABO frequencies with published data for the United Arab Emirates (UAE), as well as international and historical ABO data on dialysis frequency. Although there was an apparent protective effect of blood group O when we compared blood group frequencies with the UAE data, this disappeared when corrected for ethnicity. We concluded that any association of the ABO blood group with COVID-19 infection is unlikely to be of major importance and should not be used to reassure patients that they are mildly protected against COVID-19 without vaccination.

OBJECTIVES:High dietary phosphate intake may lead to adverse outcomes including cardiovascular disease (CVD). Urinary phosphate excretion, a marker of intestinal phosphate absorption, may be a more reliable marker of phosphate homeostasis in steady state than serum phosphate. Studies report good agreement between urine phosphate-to-creatinine ratio (uPiCr) and 24-hour urinary phosphate; however, whether uPiCr is associated with increased risk of CVD or mortality remains uncertain. This study aimed to assess the relationship between uPiCr and all-cause and CVD mortality.DESIGN AND METHODS:This is an observational longitudinal cohort study using data from the population-based national Australian Diabetes, Obesity and Lifestyle study (n = 10,014 participants). Non-linear association between uPiCr and all-cause and CVD mortality was assessed using fractional polynomial transformations. Cox proportional hazards regression models were used to estimate adjusted hazard ratios for all-cause and CVD mortality.RESULTS:Median age [interquartile range] was 50 [41-62] years, and 46% were male. Median uPiCr was 1.38 [1.02-1.79] mmol/mmol. Median follow-up time was 16.9 years with 1,735 deaths. uPiCr was associated with all-cause and CVD mortality in univariate models and when adjusted for age and gender. However, associations were not significant in multivariate models. Sensitivity analyses excluding participants with chronic kidney disease (CKD) revealed a significant J-shaped association between uPiCr and all-cause mortality. Urine phosphate alone showed an association with increased all-cause mortality in a similar J-shape relationship.CONCLUSION:Although no association between uPiCr and all-cause and CVD mortality was observed in multivariate analyses in the whole cohort, a significant relationship between uPiCr and mortality in those without CKD suggests that uPiCr may have predictive validity for future adverse outcomes in people with no CKD.

The effectiveness of the inactivated BBIBP-CorV vaccine against severe COVID-19 outcomes (hospitalization, critical care admission and death due to COVID-19) and its long-term effectiveness have not been well characterized among the general population. We conducted a retrospective cohort study using electronic health records of 3,147,869 adults, of which 1,099,886 vaccinated individuals were matched, in a 1:1 ratio to 1,099,886 unvaccinated persons. A Cox-proportional hazard model with time varying coefficients was used to assess the vaccine effectiveness adjusting for age, sex, comorbidity, ethnicity, and the calendar month of entry into the study. Our analysis showed that the effectiveness was 79.6% (95% CI, 77.7 to 81.3) against hospitalization, 86% (95% CI, 82.2 to 89.0) against critical care admission, and 84.1% (95% CI, 70.8 to 91.3) against death due to COVID-19. The effectiveness against these severe outcomes declined over time indicating the need for booster doses to increase protection against severe COVID-19 outcomes.

REFERENCES 1. Humphreys BD, Sharman JP, Henderson JM, et al. Gemcitabineassociated thrombotic microangiopathy. Cancer. 2004;100:2664-2670. 2. Efe O, Goyal L, Galway A, Zhu AX, Niles JL, Zonozi R. Treatment of gemcitabine-induced thrombotic microangiopathy followed by gemcitabine rechallenge with eculizumab. Kidney Int Rep. 2021;6:1464-1468. 3. Blake-Haskins JA, Lechleider RJ, Kreitman RJ. Thromboticmicroangiopathy with targeted cancer agents. Clin Cancer Res. 2011;17:5858-5866. 4. Katagiri D, Hinoshita F. Gemcitabine-induced thrombotic microangiopathy with nephrotic syndrome. CEN Case Rep. 2018;7:217-220. 5. Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol. 2018;13:300-317.