Successful simultaneous liver-kidney transplantation for renal failure associated with hereditary complement C3 deficiency.

Hereditary complement C3 deficiency is associated with recurrent bacterial infections and proliferative glomerulonephritis. We describe a case of an adult with complete deficiency of complement C3 due to homozygous mutations in C3 gene: c.1811delT (Val604Glyfs*2), recurrent bacterial infections, crescentic glomerulonephritis, and end-stage renal failure. Following isolated kidney transplantation he would remain C3 deficient with a similar, or increased, risk of infections and glomerulonephritis. As C3 is predominantly synthesized in the liver, with a small proportion of C3 monocyte derived and kidney derived, he proceeded to simultaneous liver-kidney transplantation. The procedure has been successful with restoration of his circulating C3 levels, normal liver and kidney function at 26 months of follow-up. Simultaneous liver-kidney transplant is a viable option to be considered in this rare setting.

Distinct functions of diaphanous-related formins regulate HIV-1 uncoating and transport.

Diaphanous (Dia)-related formins (DRFs) coordinate cytoskeletal remodeling by controlling actin nucleation and microtubule (MT) stabilization to facilitate processes such as cell polarization and migration; yet the full extent of their activities remains unknown. Here, we uncover two discrete roles and functions of DRFs during early human immunodeficiency virus type 1 (HIV-1) infection. Independent of their actin regulatory activities, Dia1 and Dia2 facilitated HIV-1-induced MT stabilization and the intracellular motility of virus particles. However, DRFs also bound in vitro assembled capsid-nucleocapsid complexes and promoted the disassembly of HIV-1 capsid (CA) shell. This process, also known as "uncoating," is among the most poorly understood stages in the viral lifecycle. Domain analysis and structure modeling revealed that regions of Dia2 that bound viral CA and mediated uncoating as well as early infection contained coiled-coil domains, and that these activities were genetically separable from effects on MT stabilization. Our findings reveal that HIV-1 exploits discrete functions of DRFs to coordinate critical steps in early infection and identifies Dia family members as regulators of the poorly understood process of HIV-1 uncoating.

Spatiotemporal Control of CRISPR/Cas9 Function in Cells and Zebrafish using Light-Activated Guide RNA.

We developed a new method for the conditional regulation of CRISPR/Cas9 activity in mammalian cells and zebrafish embryos using photochemically activated, caged guide RNAs (gRNAs). Caged gRNAs are generated by substituting four nucleobases evenly distributed throughout the 5'-protospacer region with caged nucleobases during synthesis. Caging confers complete suppression of gRNA:dsDNA-target hybridization and rapid restoration of CRISPR/Cas9 function upon optical activation. This tool offers simplicity and complete programmability in design, high spatiotemporal specificity in cells and zebrafish embryos, excellent off-to-on switching, and stability by preserving the ability to form Cas9:gRNA ribonucleoprotein complexes. Caged gRNAs are novel tools for the conditional control of gene editing, thereby enabling the investigation of spatiotemporally complex physiological events by obtaining a better understanding of dynamic gene regulation.

Base pairing and structural insights into the 5-formylcytosine in RNA duplex.

5-Formylcytidine (f(5)C), a previously discovered natural nucleotide in the mitochondrial tRNA of many species including human, has been recently detected as the oxidative product of 5-methylcytidine (m(5)C) through 5-hydroxymethylcytidine (hm(5)C) in total RNA of mammalian cells. The discovery indicated that these cytosine derivatives in RNA might also play important epigenetic roles similar as in DNA, which has been intensively investigated in the past few years. In this paper, we studied the base pairing specificity of f(5)C in different RNA duplex contexts. We found that the 5-formyl group could increase duplex thermal stability and enhance base pairing specificity. We present three high-resolution crystal structures of an octamer RNA duplex [5'-GUA(f(5)C)GUAC-3']2 that have been solved under three crystallization conditions with different buffers and pH values. Our results showed that the 5-formyl group is located in the same plane as the cytosine base and forms an intra-residue hydrogen bond with the amino group in the N4 position. In addition, this modification increases the base stacking between the f(5)C and the neighboring bases while not causing significant global and local structure perturbations. This work provides insights into the effects of 5-formylcytosine on RNA duplex.

Agonist-induced platelet procoagulant activity requires shear and a Rac1-dependent signaling mechanism.

Activated platelets facilitate blood coagulation by exposing phosphatidylserine (PS) and releasing microvesicles (MVs). However, the potent physiological agonists thrombin and collagen poorly induce PS exposure when a single agonist is used. To obtain a greater procoagulant response, thrombin is commonly used in combination with glycoprotein VI agonists. However, even under these conditions, only a percentage of platelets express procoagulant activity. To date, it remains unclear why platelets poorly expose PS even when stimulated with multiple agonists and what the signaling pathways are of soluble agonist-induced platelet procoagulant activity. Here we show that physiological levels of shear present in blood significantly enhance agonist-induced platelet PS exposure and MV release, enabling low doses of a single agonist to induce full-scale platelet procoagulant activity. PS exposed on the platelet surface was immediately released as MVs, revealing a tight coupling between the 2 processes under shear. Using platelet-specific Rac1(-/-) mice, we discovered that Rac1 plays a common role in mediating the low-dose agonist-induced procoagulant response independent of platelet aggregation, secretion, and the apoptosis pathway. Platelet-specific Rac1 function was not only important for coagulation in vitro but also for fibrin accumulation in vivo following laser-induced arteriolar injury.

Total Cyanide Field Spikes for Industrial Wastewater Samples Verify Successful Sample Integrity, Preservation, Pre-Treatment and Testing.

Obtaining accurate and precise results for total cyanide concentrations in wastewater samples is fraught with positive and negative interferences. Even the United States Environmental Protection Agency has acknowledged that it may be difficult or impossible to adequately mitigate all interferences. We demonstrated that a field spike of complex cyanide can be successfully used to demonstrate when sampling, preservation, pre-treatment, and analysis techniques are working adequately to retain any cyanide present in the sample without causing false positives or false negatives. For 257 industrial wastewater effluent samples collected at a wide variety of Greater Boston industries, 237 (92.2%) had usable field spike recoveries, averaging 86.2% recovery. Field spike recoveries for problematic industries that had very high or very low field spike recoveries were useful to show when alternative preservations and field dilutions were successfully preserving total cyanide. The field spike approach is general and should also work in a similar manner for raw and treated drinking water samples.

Observing the earth from space: Does a virtual reality overview effect experience increase pro-environmental behaviour?

Astronauts (and recently businessmen) often express a renewed sense of responsibility for taking care of the environment, after observing the overwhelming beauty of Earth from space. Despite recent attention for this "overview effect", it is unclear whether experiencing the effect directly impacts pro-environmental behaviour. Using a virtual reality experience, the current research tests in two experimental studies the direct impact of an immersive overview effect experience on both short-term and longer term subsequent pro-environmental behaviours (donating to an environmental NGO, consuming less diary and meat). Furthermore, it investigates whether the technological immersiveness of the VR experience amplifies the effect, and the mediating role of connectedness to nature. Results show no effects of the short (7 minutes) overview effect VR video on pro-environmental behaviour (Study 1). For the longer video (15 minutes, Study 2), the results showed that the most immersive experience (video featuring meditative music and voice-over) appeared to increase connection with nature and higher donation amounts to an eco-NGO, but not significantly. No effects were found for subsequent meat and dairy consumption behaviours (measured on day 2, 4, and 6). These findings contribute to a deeper understanding of the specific features determining the effectiveness of the overview effect experiences on actual pro-environmental behaviour, providing important insights to businesses and educational institutions.

Accuracy of the MDRD (Modification of Diet in Renal Disease) study and CKD-EPI (CKD Epidemiology Collaboration) equations for estimation of GFR in the elderly.

BACKGROUND: Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated using equations that adjust serum creatinine concentration for age, race, and sex. The Modification of Diet in Renal Disease (MDRD) Study equation is widely used, but underestimates GFR at higher levels. The serum creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI(cr)) equation generally provides more accurate estimation at GFR >60 mL/min/1.73 m(2). Newer equations have been reported using cystatin C concentration either alone (CKD-EPI(cys)) or in combination with creatinine concentration (CKD-EPI(cr-cys)). None of these equations has been well validated in older people. We tested the accuracy of these equations in people 74 years or older compared with GFR measured by a reference method. STUDY DESIGN: Diagnostic test evaluation in a prospective cohort. SETTING & PARTICIPANTS: Participants (n = 394; median age, 80 [range, 74-97] years) recruited from nephrology clinics and the community. INDEX TEST: GFR estimated using the MDRD Study, CKD-EPI(cr), CKD-EPI(cys) and CKD-EPI(cr-cys) equations. REFERENCE TEST: GFR measured using an iohexol clearance method. RESULTS: Median measured GFR was 53.4 (range, 7.2-100.9) mL/min/1.73 m(2). MDRD Study-, CKD-EPI(cr)-, and CKD-EPI(cr-cys)-estimated GFRs overestimated GFR (median differences of 3.5 [P< 0.001], 1.7 [P < 0.001], and 0.8 [P = 0.02] mL/min/1.73 m(2), respectively); the CKD-EPI(cys) equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR [P(30)]) was 81%, 83%, 86%, and 86% for the MDRD Study, CKD-EPI(cr), CKD-EPI(cys), and CKD-EPI(cr-cys) equations, respectively. Accuracy of the MDRD Study equation was inferior (P = 0.004) to the CKD-EPI(cr) equation at GFR >60 mL/min/1.73 m(2). LIMITATIONS: Those of non-European ancestry were not included. For practical reasons, only a 4-hour sampling protocol was used for iohexol clearance. CONCLUSIONS: The CKD-EPI(cr) equation appeared less biased and was more accurate than the MDRD Study equation. No equation achieved an ideal P(30) in the overall population. Our data suggest that GFR estimation is as satisfactory in older people of European ancestry as it has been reported to be in younger individuals.

Bone-specific alkaline phosphatase concentrations are less variable than those of parathyroid hormone in stable hemodialysis patients.

Abnormalities of bone mineral metabolism and vascular calcification are prevalent in patients with kidney failure. Clinical management is based on biochemical targets, in particular parathyroid hormone (PTH) concentrations, but this has many limitations including high biological variation. A possible alternative is bone-specific alkaline phosphatase (ALP); therefore, we evaluated the biological variation of this marker in patients undergoing hemodialysis. Bone ALP was measured in non-fasting serum samples taken twice a week over a 6-week period in 22 stable hemodialysis patients and 12 healthy volunteers. The within-individual coefficients of variance were calculated and used to derive the critical difference required to be certain that an observed change was significant. The coefficient of variance for bone ALP was significantly higher in hemodialysis patients compared to healthy individuals. Seven samples were required to estimate the homeostatic set point of bone ALP, within 10%, in a hemodialysis patient. The concentration of serial bone ALP measurements would need to change by 36% between any two measurements before it can be considered a significant change. Since the biological variation of bone ALP is less than half that reported for PTH, our study provides further support for the use of bone ALP as an alternative marker of bone mineral metabolism in the setting of chronic kidney disease-mineral and bone disorder.

The effect of dialysis modality on phosphate control : haemodialysis compared to haemodiafiltration. The Pan Thames Renal Audit.

BACKGROUND AND OBJECTIVES: Hyperphosphataemia is a primary risk factor for patients with end-stage kidney failure. Phosphate clearance by traditional thrice-weekly standard haemodialysis is inadequate for patients achieving recommended dietary protein goals. We investigated whether phosphate control was improved by adding convective clearance with haemodiafiltration. METHODS: We audited pre-midweek session calcium and phosphate levels in 5366 adult patients, 4515 treated by haemodialysis and 851 by on-line haemodiafiltration. RESULTS: The cohorts were similar for age, sex and dialysis vintage. Serum phosphate was lower in the haemodiafiltration cohort (1.42 +/- 0.61 mmol/l) compared to the haemodialysis cohort (1.53 +/- 0.53 mmol/l; P < 0.001), as was the calcium-phosphate product (3.31 +/- 1.53 vs 3.5 +/- 1.33 mmol(2)/l(2), respectively; P < 0.001) despite a shorter treatment session time (3.68 +/- 0.44 vs 3.92 +/- 0.49 h; P < 0.001). Parathyroid hormone levels were similar. CONCLUSIONS: The results of this audit suggest that haemodiafiltration offers improved phosphate control compared to standard intermittent haemodialysis.

Do differences in dialysis prescription impact on KDOQI bone mineral targets? The Pan Thames Renal Audit.

BACKGROUND AND OBJECTIVES: Patients achieving the Kidney Disease Outcomes Quality Initiative (KDOQI) bone mineral clinical practice guidelines have been reported to have improved survival. Many factors affecting calcium and phosphate control are not modifiable; however, we wished to determine whether differences in dialysis treatment could affect achievement of KDOQI clinical guideline targets. METHODS: We audited pre-mid-week session calcium and phosphate levels in 5,324 adult patients receiving thrice weekly dialysis in the 14 Pan Thames centres: 60% male, mean age 62 ± 16 years, median dialysis vintage 29 months (14-58), 84% treated by haemodialysis, 16% by online haemodiafiltration, median session time 4.0 h (3.5-4.0). RESULTS: Patients achieving the KDOQI guidelines varied between the centres: 23.4-60% for calcium, 31.7-56.7% for phosphate, 60-87.3% for calcium-phosphate product, 17.1-46.8% for parathyroid hormone (PTH) and 1.8-10.8% for all 4 targets. Those centres which used the highest dialysate calcium concentrations (1.5 mmol/l, 3 mEq/l) had more patients above the KDOQI serum calcium and more below the PTH target, than those centres using the lowest calcium dialysates (1 mmol/l, 2 mEq/l), with χ(2) = 85.1 and χ(2) = 52.4, p < 0.001, respectively. On logistic regression analysis, serum phosphate was negatively associated with duration of dialysis session time (F = 21.4, p = 0.000) and haemodiafiltration (F = 9.6, p = 0.000), respectively. CONCLUSIONS: Although many of the factors determining calcium and phosphate control in haemodialysis patients are unmodifiable, dialysate calcium concentration, the duration of the dialysis session and haemodiafiltration all had an impact on calcium, phosphate and PTH.

Synthesis and investigation of the 5-formylcytidine modified, anticodon stem and loop of the human mitochondrial tRNAMet.

Human mitochondrial methionine transfer RNA (hmtRNA(Met)(CAU)) has a unique post-transcriptional modification, 5-formylcytidine, at the wobble position-34 (f(5)C(34)). The role of this modification in (hmtRNA(Met)(CAU)) for the decoding of AUA, as well as AUG, in both the peptidyl- and aminoacyl-sites of the ribosome in either chain initiation or chain elongation is still unknown. We report the first synthesis and analyses of the tRNA's anticodon stem and loop domain containing the 5-formylcytidine modification. The modification contributes to the tRNA's anticodon domain structure, thermodynamic properties and its ability to bind codons AUA and AUG in translational initiation and elongation.

Changes of NOx in urban air detected with monitoring VIS-NIR field spectrometer during the coronavirus pandemic: A case study in Germany.

The global outbreak of the coronavirus pandemic has led to a significant reduction of traffic and traffic-related urban air pollution. One important pollutant in this context is NO2. Sudden change in NO2 emissions related to reduction of urban traffic due to infection protection measures can be detected in Düsseldorf, Germany with continuous measurements of down-welling light with a RoX automated field-spectrometer. In comparison to a nearby reference instrument, a waveband around 590 nm was identified as significant for the retrieval in the VIS-NIR spectral range. A decision tree based on principal components which were decomposed from down-welling radiance spectra has been the most robust approach to retrieved NO2 values. Better differentiation of the NO2 value-range is achieved with a partial least square regression model. The results suggest that traffic-related changes of NOx pollution in urban air can be detected through continuous down-welling radiance measurements with inexpensive automated field-spectrometer systems.

Anti-Escherichia coli Functionalized Silver-Doped Carbon Nanofibers for Capture of E. coli in Microfluidic Systems.

Silver-doped carbon nanofibers (SDCNF) are used as the base material for the selective capture of Escherichia coli in microfluidic systems. Fibers were spun in a glovebox with dry atmosphere maintained by forced dry air pumped through the closed environment. This affected the evaporation rate of the solvent during the electrospinning process and the distribution of silver particles within the fiber. Antibodies are immobilized on the surface of the silver-doped polyacrylonitrile (PAN) based carbon nanofibers via a three-step process. The negatively charged silver particles present on the surface of the nanofibers provide suitable sites for positively charged biotinylated poly-(l)-lysine-graft-poly-ethylene-glycol (PLL-g-PEG biotin) conjugate attachment. Streptavidin and a biotinylated anti-E. coli antibody were then added to create anti-E. coli surface functionalized (AESF) nanofibers. Functionalized fibers were able to immobilize up to 130 times the amount of E. coli on the fiber surface compared to neat silver doped fibers. Confocal images show E. coli remains immobilized on fiber mat surface after extensive rinsing showing the bacteria is not simply a result of non-specific binding. To demonstrate selectivity and functionalization with both gram negative and gram-positive antibodies, anti-Staphylococcus aureus surface functionalized (ASSF) nanofibers were also prepared. Experiments with AESF performed with Staphylococcus aureus (S. aureus) and ASSF with E. coli show negligible binding to the fiber surface showing the selectivity of the functionalized membranes. This surface functionalization can be done with a variety of antibodies for tunable selective pathogen capture.

A Comprehensive Review of the Covalent Immobilization of Biomolecules onto Electrospun Nanofibers.

Biomolecule immobilization has attracted the attention of various fields such as fine chemistry and biomedicine for their use in several applications such as wastewater, immunosensors, biofuels, et cetera. The performance of immobilized biomolecules depends on the substrate and the immobilization method utilized. Electrospun nanofibers act as an excellent substrate for immobilization due to their large surface area to volume ratio and interconnectivity. While biomolecules can be immobilized using adsorption and encapsulation, covalent immobilization offers a way to permanently fix the material to the fiber surface resulting in high efficiency, good specificity, and excellent stability. This review aims to highlight the various covalent immobilization techniques being utilized and their benefits and drawbacks. These methods typically fall into two categories: (1) direct immobilization and (2) use of crosslinkers. Direct immobilization techniques are usually simple and utilize the strong electrophilic functional groups on the nanofiber. While crosslinkers are used as an intermediary between the nanofiber substrate and the biomolecule, with some crosslinkers being present in the final product and others simply facilitating the reactions. We aim to provide an explanation of each immobilization technique, biomolecules commonly paired with said technique and the benefit of immobilization over the free biomolecule.

Risk of relapse of multiple myeloma following kidney transplantation.

BACKGROUND: Autologous stem cell transplantation (ASCT) and novel therapies have improved the prognosis for patients with multiple myeloma (MM). For those who undergo ASCT while on dialysis, a similar survival compared with the overall MM population has been reported. Therefore, for patients achieving remission following ASCT, kidney transplantation is an attractive option, offering an improved quality of life and significant economic advantage. METHOD: This case series investigates the outcome of five patients who underwent an ASCT for MM with subsequent kidney transplantation between 2006 and 2012. RESULTS: Four patients presented with end-stage renal disease (ESRD) and one progressed to ESRD shortly after diagnosis. Induction chemotherapy regimens with novel agents including thalidomide and bortezomib were utilized. Following attainment of very good partial remission or complete remission, high-dose melphalan ASCTs were performed after a median of 10 months. Kidney transplantation (living donor n = 3, deceased donor n = 2) with tacrolimus-based immunosuppression regimens was completed at a median of 27 months after ASCT. Patients 1 and 3 experienced relapse of myeloma at 6 and 16 months after kidney transplantation. Patients 2, 4 and 5 remain alive at 55 months (median) after kidney transplantation with no evidence of relapse. CONCLUSION: Forty percent of our cohort experienced a relapse in MM within 2 years of kidney transplantation. Death-censored graft survival and patient survival were 80% at 4 years. Our study adds to the growing literature supporting kidney transplantation following successful ASCT for MM and is useful when counselling patients regarding renal and haematological outcomes.

Symmetric dimethylarginine is a stronger predictor of mortality risk than asymmetric dimethylarginine among older people with kidney disease.

BACKGROUND: Circulating asymmetric dimethylarginine and symmetric dimethylarginine are increased in patients with kidney disease. Symmetric dimethylarginine is considered a good marker of glomerular filtration rate, while asymmetric dimethylarginine is a marker of cardiovascular risk. However, a link between symmetric dimethylarginine and all-cause mortality has been reported. In the present study, we evaluated both dimethylarginines as risk and glomerular filtration rate markers in a cohort of elderly white individuals, both with and without chronic kidney disease. METHODS: Glomerular filtration rate was measured in 394 individuals aged >74 years using an iohexol clearance method. Plasma asymmetric dimethylarginine, symmetric dimethylarginine and iohexol were measured simultaneously using isotope dilution tandem mass spectrometry. RESULTS: Plasma asymmetric dimethylarginine concentrations were increased ( P < 0.01) in people with glomerular filtration rate <60 mL/min/1.73 m2 compared with those with glomerular filtration rate ≥60 mL/min/1.73 m2, but did not differ ( P > 0.05) between those with glomerular filtration rate 30-59 mL/min/1.73 m2 and <30 mL/min/1.73 m2. Plasma symmetric dimethylarginine increased consistently across declining glomerular filtration rate categories ( P < 0.0001). Glomerular filtration rate had an independent effect on plasma asymmetric dimethylarginine concentration, while glomerular filtration rate, gender, body mass index and haemoglobin had independent effects on plasma symmetric dimethylarginine concentration. Participants were followed up for a median of 33 months. There were 65 deaths. High plasma asymmetric dimethylarginine ( P = 0.0412) and symmetric dimethylarginine ( P < 0.0001) concentrations were independently associated with reduced survival. CONCLUSIONS: Among elderly white individuals with a range of kidney function, symmetric dimethylarginine was a better marker of glomerular filtration rate and a stronger predictor of outcome than asymmetric dimethylarginine. Future studies should further evaluate the role of symmetric dimethylarginine as a marker of outcome and assess its potential value as a marker of glomerular filtration rate.

Relationship of serum cystatin C to peritoneal and renal clearance measures in peritoneal dialysis: a cross-sectional study.

BACKGROUND: Clinical management of peritoneal dialysis patients includes assessments of peritoneal and renal clearances of the low-molecular-weight endogenous solutes creatinine and urea. Cystatin C is a low-molecular-weight protein used as a glomerular filtration rate marker. We investigated whether serum cystatin C concentration is related to peritoneal and renal clearances of creatinine and urea. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 119 patients undergoing peritoneal dialysis in a single dialysis unit. PREDICTOR: Peritoneal, renal, and total clearance of urea as Kt/V(urea) and creatinine as weekly creatinine clearance (C(Cr)). Residual renal function (RRF) as the average of renal clearances of urea and creatinine. OUTCOMES & MEASUREMENTS: Serum concentrations of cystatin C measured by using a particle-enhanced nephelometric immunoassay. RESULTS: Serum cystatin C concentration was related inversely to RRF (Spearman rank correlation coefficient [r(s)] = -0.65; P < 0.001), total weekly C(Cr) (r(s) = -0.52; P < 0.001), and total Kt/V(urea) (r(s) = -0.23; P = 0.01). In a multiple regression model, weight, normalized protein catabolic rate, and RRF had independent effects on serum cystatin C concentrations. Additional multiple regression models showed that only the renal components of Kt/V(urea) and weekly C(Cr) contributed to serum cystatin C concentrations. LIMITATIONS: Absence of reference GFR method. CONCLUSIONS: Serum cystatin C concentrations reflect predominantly renal, not peritoneal, clearance. Serum cystatin C measurement may be a simple and practical alternative to measurement of RRF.

Bone mineral metabolism and its relationship to kidney disease in a residential care home population: a cross-sectional study.

BACKGROUND: Institutionalized older people have a high risk of bone fractures due to osteoporosis. In addition, chronic kidney disease (CKD) is highly prevalent in older people living in residential homes. Secondary hyperparathyroidism, poor calcium intake and deficiency of 1,25-dihydroxyvitamin D may lead to decreased bone mass in people with CKD. The present cross-sectional study assessed the relationship between markers of bone mineral metabolism and kidney function in a residential care home population. METHODS: Older subjects were recruited from residential care homes and kidney function stratified by the estimated glomerular filtration rate (GFR). Parathyroid hormone (PTH), 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 188 residents not receiving vitamin D/calcium treatment [mean age 85 (range 68- 100) years, 75% female] and in 52 residents receiving vitamin D/calcium supplementation. RESULTS: Amongst those not receiving vitamin D/calcium, median PTH increased with declining GFR (P < 0.0001), particularly as GFR (mL/min/1.73 m(2)) fell below 45. PTH concentration was suppressed by increasing 25-hydroxyvitamin D (P < 0.0001), but not 1,25-dihydroxyvitamin D (P > 0.05) concentration. Nearly all residents (92%) had 25-hydroxyvitamin D deficiency or insufficiency and this was uninfluenced by kidney function (P > 0.05). Concentration of 1,25-dihydroxyvitamin D declined with worsening renal function (P < 0.0004) but 1,25-dihydroxyvitamin D deficiency was prevalent at all stages of kidney disease, including amongst residents receiving vitamin D/calcium supplementation. CONCLUSION: Vitamin D deficiency and secondary hyperparathyroidism are common in this population irrespective of renal function. However, as GFR falls below 45, the prevalence of secondary hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency increases. Unidentified CKD appears to exacerbate secondary hyperparathyroidism in this at risk population.