Phosphatonins: From Discovery to Therapeutics.

OBJECTIVE: Phosphate is crucial for cell signaling, energy metabolism, nucleotide synthesis, and bone mineralization. The gut-bone-parathyroid-kidney axis is influenced by parathyroid hormone, 1,25-dihydroxyvitamin D, and phosphatonins, especially fibroblast growth factor 23 (FGF23). These hormones facilitate maintenance of phosphate homeostasis. This review summarizes current knowledge regarding the phosphate homeostasis, phosphatonin pathophysiology, and clinical implications of FGF23-related hypophosphatemic disorders, with specific focus on burosumab treatment. METHOD: A focused literature search of PubMed was conducted. RESULTS: Phosphatonins including FGF23, secreted frizzled-related protein 4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 7 play a pathogenic role in several hypophosphatemic disorders. Excess FGF23 inhibits sodium-dependent phosphate cotransporters (NaPi-2a and NaPi-2c), resulting in hyperphosphaturia and hypophosphatemia. Additionally, FGF23 suppresses 1,25-dihydroxyvitamin D synthesis in the proximal renal tubule, and thus, it indirectly inhibits intestinal phosphate absorption. Disorders of FGF23-related hypophosphatemia include X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia/McCune-Albright syndrome, and tumor-induced osteomalacia (TIO). Complications of conventional therapy with oral phosphate and vitamin D analogs comprise gastrointestinal distress, hypercalcemia, nephrocalcinosis, and secondary/tertiary hyperparathyroidism. In both children and adults with XLH and TIO, the anti-FGF23 antibody burosumab exhibits a favorable safety profile and is associated with healing of rickets in affected children and improvement of osteomalacia in both children and adults. CONCLUSION: The treatment paradigm for XLH and TIO is changing based on data from recent clinical trials. Research suggest that burosumab is effective and safe for pediatric and adult patients with XLH or TIO.

High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity.

Full-length parathyroid hormone (PTH 1-84) is crucial for the regulation of calcium and phosphate homeostasis and bone remodeling. PTH 1-84 is metabolized into various PTH fragments, which are measured with varying levels of efficiency by PTH immunoassays. These PTH fragments, which increase in serum as CKD progresses, could potentially modulate the effects of PTH 1-84 and contribute to CKD-associated bone disorders. To obtain a true biologic representation of total PTH bioactivity, it is necessary to measure not only PTH 1-84 but also PTH fragments that are present in circulation. Traditional second-generation PTH immunoassays collectively measure PTH 1-84, PTH fragments, and post-translationally modified PTH 1-84, making it difficult to accurately predict the character of underlying renal osteodystrophy. This review highlights current advances in methods available for PTH measurement and the clinical relevance of PTH fragments in CKD. We emphasize the usefulness of mass spectrometry as a potential reference method for PTH measurement.

Short carboxyl terminal parathyroid hormone peptides modulate human parathyroid hormone signaling in mouse osteoblasts.

BACKGROUND: Novel human parathyroid hormone (hPTH) peptides of unknown biological activity have recently been identified in the serum of subjects with normal renal function, chronic renal failure, and end-stage renal disease through the application of liquid chromatography-high resolution mass spectrometry. PURPOSE: of experiments: To determine the bioactivity of these peptides, we synthesized hPTH28-84, hPTH38-84, and hPTH45-84 peptides by solid phase peptide synthesis and tested their bioactivity in MC3T3-E1 mouse osteoblasts, either individually or together with the native hormone, hPTH1-84, by assessing the accumulation of 3´,5´-cyclic adenosine monophosphate (cAMP) and the induction of alkaline phosphatase activity. RESULTS: Increasing doses of hPTH1-84 (1-100 nM) increased the accumulation of cAMP and alkaline phosphatase activity in osteoblasts. hPTH28-84, hPTH38-84, and hPTH45-84 in concentrations of 1-100 nM were biologically inert. Surprisingly, 100 nM hPTH38-84 and hPTH45-84 increased the accumulation of cAMP in osteoblasts treated with increasing amounts of hPTH1-84. Human PTH28-84 had no effects on cAMP activity alone or in combination with hPTH1-84. Conversely, 100 nM hPTH38-84, hPTH45-84, and hPTH28-84 blocked the activation of alkaline phosphatase activity by hPTH1-84. CONCLUSIONS: The data show that the short carboxyl-terminal hPTH peptides, hPTH38-84 and hPTH45-84, increase the amount of cellular cAMP generated in cultured osteoblasts in response to treatment with full-length hPTH1-84 when compared to full-length hPTH1-84 alone. Human PTH28-84 had no effect on cAMP activity alone or in combination with hPTH1-84. Human PTH28-84, hPTH38-84 and hPTH45-84 reduced the effects of hPTH1-84 in osteoblasts with respect to the induction of alkaline phosphatase activity compared to hPTH1-84 alone. Short carboxyl peptides of human PTH are biologically inert but when administered together with full-length hPTH1-84 modulate the bioactivity of hPTH1-84 in osteoblasts.

Chemical Characterization and Quantification of Circulating Intact PTH and PTH Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure.

BACKGROUND: The precise concentrations of full-length parathyroid hormone (PTH1-84) and the identity and concentrations of PTH fragments in patients with various stages of chronic renal failure are unknown. METHODS: We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to characterize and quantify PTH1-84 and PTH fragments in serum of 221 patients with progressive renal dysfunction. Following capture by matrix-bound amino-terminal or carboxyl-terminal region-specific antibodies and elution from matrix, PTH1-84 and PTH fragments were identified and quantitated using LC-HRMS. PTH was simultaneously measured using an intact PTH (iPTH) immunoassay. RESULTS: Full-length PTH1-84 and 8 PTH fragments (PTH28-84, 34-77, 34-84, 37-77, 37-84, 38-77, 38-84, and 45-84) were unequivocally identified and were shown to increase significantly when an eGFR declined to ≤17-23 mL/min/1.73m2. Serum concentrations of PTH1-84 were similar when measured by LC-HRMS following capture by amino-terminal or carboxyl-terminal immunocapture methods. In patients with an eGFR of <30 mL/min/1.73 m2, serum PTH concentrations measured using LC-HRMS were significantly lower than PTH measured using an iPTH immunoassay. PTH7-84 and oxidized forms of PTH1-84 were below the limit of detection (30 and 50 pg/mL, respectively). CONCLUSIONS: LC-HRMS identifies circulating PTH1-84, carboxyl-terminal PTH fragments, and mid-region PTH fragments, in patients with progressive renal failure. Serum PTH1-84 and its fragments markedly rise when an eGFR decreases to ≤17-23 mL/min/1.73 m2. PTH concentrations measured using LC-HRMS tend to be lower than those measured using an iPTH immunoassay, particularly in severe chronic renal failure. Our data do not support the existence of circulating PTH7-84 and oxidized PTH1-84.

Phosphate as a Signaling Molecule.

Phosphorus plays a vital role in diverse biological processes including intracellular signaling, membrane integrity, and skeletal biomineralization; therefore, the regulation of phosphorus homeostasis is essential to the well-being of the organism. Cells and whole organisms respond to changes in inorganic phosphorus (Pi) concentrations in their environment by adjusting Pi uptake and altering biochemical processes in cells (local effects) and distant organs (endocrine effects). Unicellular organisms, such as bacteria and yeast, express specific Pi-binding proteins on the plasma membrane that respond to changes in ambient Pi availability and transduce intracellular signals that regulate the expression of genes involved in cellular Pi uptake. Multicellular organisms, including humans, respond at a cellular level to adapt to changes in extracellular Pi concentrations and also have endocrine pathways which integrate signals from various organs (e.g., intestine, kidneys, parathyroid glands, bone) to regulate serum Pi concentrations and whole-body phosphorus balance. In mammals, alterations in the concentrations of extracellular Pi modulate type III sodium-phosphate cotransporter activity on the plasma membrane, and trigger changes in cellular function. In addition, elevated extracellular Pi induces activation of fibroblast growth factor receptor, Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) and Akt pathways, which modulate gene expression in various mammalian cell types. Excessive Pi exposure, especially in patients with chronic kidney disease, leads to endothelial dysfunction, accelerated vascular calcification, and impaired insulin secretion.

Hyperphosphatemia with elevated serum PTH and FGF23, reduced 1,25(OH)2D and normal FGF7 concentrations characterize patients with CKD.

BACKGROUND: Hyperphosphatemia confers adverse cardiovascular outcomes, and commonly occurs in late-stage CKD. Fibroblast growth factor 7 (FGF7) is a phosphaturic peptide which decreases renal phosphate transport in vitro and in vivo. Serum FGF7 concentrations are reduced in hyperphosphatemic patients with hypophosphatasia and are elevated in some hypophosphatemic patients with tumor-induced osteomalacia. No data, however, are available on whether circulating FGF7 concentrations increase to compensate for phosphate retention in CKD patients. METHODS: This was a cross-sectional study performed among 85 adult patients with varying estimated glomerular filtration rates (eGFR). We measured serum intact FGF7 (iFGF7) concentration using an iFGF7 immunoassay and determined its associated factors. Relationships between eGFR and mineral metabolism biomarkers [phosphate, iFGF7, iFGF23, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25(OH)2D)] were explored. RESULTS: For eGFRs of ≥ 60 (n = 31), 45-59 (n = 16), 30-44 (n = 11), 15-29 (n = 15), and < 15 mL/min/1.73 m2 (n = 12), median (IQ25-75) iFGF7 concentrations were 46.1 (39.2-56.9), 43.1 (39.0-51.5), 47.3 (38.3-66.5), 47.7 (37.7-55.8), and 49.6 (42.5-65.6) pg/mL, respectively (P = 0.62). Significant increases in serum iFGF23, PTH, and phosphate were observed at eGFRs of < 33 (95 % CI, 26.40-40.05), < 29 (95 % CI, 22.51-35.36), and < 22 mL/min/1.73 m2 (95 % CI, 19.25-25.51), respectively, while significant decreases in serum 1,25(OH)2D were observed at an eGFR of < 52 mL/min/1.73 m2 (95 % CI, 42.57-61.43). No significant correlation was found between serum iFGF7 and phosphate, iFGF23, PTH or 1,25(OH)2D. In multivariable analyses, body mass index (per 5 kg/m2 increase) was independently associated with the highest quartile of serum iFGF7 concentration (OR, 1.20; 95 % CI, 1.12-1.55). CONCLUSIONS: Compensatory decreases in circulating 1,25(OH)2D and increases in circulating iFGF23 and PTH, but not iFGF7, facilitate normalization of serum phosphate concentration in early stages of CKD. Whether other circulating phosphaturic peptides change in response to phosphate retention in CKD patients deserves further study.

Incidence of and risk factors for post-parathyroidectomy hungry bone syndrome in patients with secondary hyperparathyroidism.

BACKGROUND: Hungry bone syndrome (HBS) following parathyroidectomy is associated with severe hypocalcemia and increased morbidity. This study aims to determine the incidence and risk factors of post-parathyroidectomy HBS in dialysis patients with secondary hyperparathyroidism (SHPT). METHODS: A retrospective cohort study was conducted, and medical records of patients with SHPT requiring parathyroidectomy between January 2014 and January 2020 were reviewed. HBS was defined as the requirement of intravenous calcium administration due to hypocalcemia-related symptoms and/or reductions in serum calcium concentration (<8.4 mg/dL) within 72 h after parathyroidectomy. RESULTS: A total of 130 dialysis patients were enrolled. The majority of patients (85.4%) received hemodialysis and the remaining patients (14.6%) received peritoneal dialysis. Ectopic parathyroid glands were identified in 6.6% of patients by preoperative parathyroid scintigraphy. Diffuse parathyroid hyperplasia was the most common histopathological characteristic of SHPT (90.8%). HBS occurred in 82.3% of patients following parathyroidectomy. Preoperative serum intact parathyroid hormone (iPTH) concentration was significantly correlated with serum calcium (r = -0.48, p < 0.01) and alkaline phosphatase (ALP) concentration (r = 0.71, p < 0.01). Patients with HBS had significantly longer hospital stays than patients without (8 versus 3 days, p < 0.01). Based on multiple logistic regression analysis, young age (≤45 years), high preoperative serum ALP (>420 IU/L) and iPTH (>1,000 pg/mL), and absence of preoperative hypercalcemia (>10.2 mg/dL) were significantly associated with HBS. CONCLUSIONS: Post-parathyroidectomy HBS is common in dialysis patients with SHPT. Young age, high preoperative serum ALP and iPTH, and low preoperative serum calcium concentrations were important risk factors for HBS.

Therapeutic concentration achievement and allograft survival comparing usage of conventional tacrolimus doses and CYP3A5 genotype-guided doses in renal transplantation patients.

AIMS: Although cytochromeP450(CYP)3A5 gene polymorphism affects personalized tacrolimus doses, there is no consensus as to whether CYP3A5 genotypes should be determined to adjust the doses. The aims were to compare the therapeutic ranges and clinical outcomes between the conventional and genotype-guided tacrolimus doses. METHODS: This randomized controlled study compared 63 cases of the conventional tacrolimus dose group (0.1 mg/kg/day) with 62 cases of the genotype-guided doses group of 0.125, 0.1 and 0.08 mg/kg for CYP3A5*1/*1, *1/*3, and *3/*3 genotypes for the initial 3 days of kidney transplantation. After day 3, dose adjustment occurred in both groups to achieve therapeutic concentrations. RESULTS: The genotype-guided group had an increased proportion of patients with tacrolimus concentrations in the therapeutic range at the steady state on day 3 (40.3 vs 23.8%, P = .048). A lower proportion of over-therapeutic concentration patients was noted in the genotype-guided group in the CYP3A5*3/*3 genotype (9.7 vs 27%, P = .013). Unexpectedly, more delayed graft functions (DGFs) were in the genotype-guided group (41.9 vs 22.2%, P = .018) especially in the CYP3A5*1/*1 participants who might have had an aggravated DGF by a longer ischaemic time and higher serum donor creatinine levels than in the control group. There were no significant differences of glomerular filtration rates or graft or patient survivals over a median 37-month follow-up period. CONCLUSIONS: Determination of the CYP3A5 genotype improved therapeutic range achievement. CYP3A5*1/*1 patients who have high risks of DGF should be closely monitored because of an increased risk of DGF and reduced glomerular filtration rate with high tacrolimus doses.

The Impact of New-Onset Diabetes Mellitus and Hypertension on All-Cause Mortality in an Apparently Healthy Population: A Ten-Year Follow-Up Study.

INTRODUCTION: The comparative effect of new-onset diabetes mellitus (DM) and hypertension (HT) on long-term mortality is a matter of debate. MATERIALS AND METHODS: From 2007 to 2017, a 10-year longitudinal retrospective cohort study was conducted in Thailand's tertiary care setting. As baseline data, health check-up data from apparently healthy participants without underlying disease from 2007 were extracted. The vital status of all participants was determined in 2017, ten years after an initial examination. The impact of new-onset DM and HT at baseline on 10-year all-cause mortality was investigated using multivariable logistic regression analysis. RESULTS: The prevalence of new-onset DM and HT was 6.4% and 28.8%, respectively, at baseline. Newly diagnosed diabetes increased the risk of all-cause mortality over 10 years (adjusted OR 4.77 and 95% CI 2.23-9.99). HT, on the other hand, did not increase the risk of death (adjusted OR 1.24 and 95% CI 0.65-2.35). Different HT and DM status combinations were compared to a nondiabetic, nonhypertensive reference. Individuals who were diabetic and hypertensive had a greater risk of death (adjusted OR 6.22 and 95% CI 2.22-17.00). Having DM without HT also increased the risk of death (adjusted OR 4.36 and 95% CI 1.35-12.87). However, having HT without DM did not result in a significant increase in 10-year mortality risk (adjusted OR 1.21 and 95% CI 0.57-2.56). CONCLUSION: In an apparently healthy population, new-onset DM is more strongly associated with 10-year all-cause mortality than new-onset HT. Having both DM and HT was associated with a greater risk of death when compared to having DM or HT alone.

Colistin-Induced Acute Kidney Injury and the Effect on Survival in Patients with Multidrug-Resistant Gram-Negative Infections: Significance of Drug Doses Adjusted to Ideal Body Weight.

BACKGROUND: Colistin is a lifesaving treatment for multidrug-resistant Gram-negative bacterial (MDR-GNB) infections along with its well-known nephrotoxicity. The controversy of colistin-induced acute kidney injury (AKI) on mortality is noted. This study aimed to determine the risk factors and impact of AKI on the survival and significance of colistin dosage. METHODS: A retrospective cohort study was performed in adult patients who received intravenous colistin for MDR-GNB treatment between June 2015 and June 2017. Factors influencing colistin-induced AKI and survival were evaluated by Cox regression analysis. Cut-off levels of the colistin dose per ideal body weight (IBW) that significantly affected clinical outcomes were assessed with linearity trends and receiver operating characteristic analyses. RESULTS: AKI occurred in 68.5% of 412 enrolled patients with an incidence rate of 10.6 per 100 patients-days and a median time was 6 (3-13) days. Stages I-III of AKI were 38.3, 24.5, and 37.2%. Factors associated with colistin-induced AKI were advanced age, high serum bilirubin, AKI presented before colistin administration, increased daily colistin doses per IBW, and concomitant use of nephrotoxic drugs. Colistin-induced AKI was related to mortality (HR 1.74, 95% CI 1.06-2.86, p=0.028). In the non-AKI before colistin usage subgroup, the total dose and total dose/IBW were >1,500-2,000 mg and 30-35 mg/kg to benefit mortality reduction but were <2,500-3,000 mg and 45-50 mg/kg for risk reduction of AKI. A daily colistin dose/IBW >4.5 mg/kg/day also increased the risk of AKI. In the AKI developed before colistin subgroup, the cut-off values of total colistin dose >1250-1350 mg and total dose/IBW >23.5-24 mg/kg demonstrated significant risks of AKI. CONCLUSION: The incidence of AKI after colistin administration was high and impacted mortality. Prevention and early correction of these related factors are mandatory. Careful use of colistin was also both beneficial in mortality and AKI reductions.

Elevated Serum Uric Acid is Associated with Rapid Decline in Kidney Function: A 10-Year Follow-Up Study.

PURPOSE: The long-term impact of changes in serum uric acid (SUA) concentration on the estimated glomerular filtration rate (eGFR) among the general population remains unclear. We investigated the longitudinal associations between changes in SUA and eGFR over 10 years in 1222 participants with baseline eGFR ≥60 mL/min/1.73 m2. METHODS: This was a 10-year retrospective cohort study conducted from 2007 to 2017. Rapid eGFR decline (defined as the highest quartile of change in eGFR between 2007 and 2017) and new-onset kidney disease (defined as an eGFR <60 mL/min/1.73 m2 at a 10-year follow-up) were examined using multiple logistic regression analysis, adjusted for sex, age, body mass index, systolic blood pressure, SUA, fasting plasma glucose, serum total cholesterol, and triglyceride at baseline. RESULTS: SUA was inversely correlated with eGFR, and the slopes of the SUA-eGFR regression lines were consistently steeper in females than males. A significant inverse correlation was also observed between 10-year changes in SUA and eGFR in both sexes. Multivariate analysis showed that every 1 mg/dL increase in SUA from baseline was associated with higher risk of rapid eGFR decline and new-onset kidney disease (OR 1.25; 95% CI 1.14-1.33 and OR 1.40; 95% CI 1.26-1.49, respectively). Furthermore, the subjects in the highest SUA quartile (>6.0 mg/dL) had a 2.45 times higher risk of rapid eGFR decline (95% CI 1.51-3.42) compared to those in the lowest SUA quartile (<3.9 mg/dL). CONCLUSION: Elevated baseline SUA is an independent risk factor for rapid eGFR decline and new-onset kidney disease in the general population.

Parathyroid Hormone Measurement in Chronic Kidney Disease: From Basics to Clinical Implications.

Accurate measurement of parathyroid hormone (PTH) is crucial for therapeutic decision-making in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). The second-generation PTH assays, often referred to as "intact PTH" assays, are the current standard and most available assays in clinical practice. However, intact PTH assays measure both full-length biologically active PTH and heterogeneous PTH fragments in the circulation, providing the equivocal value of PTH measurement in patients with CKD-MBD. Due to the variability of PTH assays, preanalytical sample errors, and the phenomenon of end-organ PTH hyporesponsiveness, current CKD-MBD guidelines recommend a wide range for serum PTH targets (2-9 the upper normal limit of the intact PTH assay) in dialysis patients to diminish the risk of developing adynamic bone disease. Nevertheless, a sizeable proportion of CKD patients still experience renal osteodystrophy despite having serum PTH levels within the recommended range. The primary cause of this inconsistency is the analytical interference of various PTH fragments and oxidized PTH forms that considerably accumulate in CKD patients. Therefore, a new mass spectrometry-based assay, which is capable of specifically measuring the whole spectra of PTH fragments, can potentially improve diagnostic accuracy for renal osteodystrophy. However, the effects of different PTH fragments on bone metabolism, vascular calcification, and mortality in CKD patients warrant further research.

Pseudohyperphosphatemia in a patient with relapsed multiple myeloma after bone marrow transplantation: A case report.

Pseudohyperphosphatemia is a laboratory artifact characterized by falsely elevated serum phosphate mostly due to paraprotein interference on the conventional automated analyzer. Clinician recognition of this phenomenon and pre-analytical preparation, including dilution or protein precipitation, can obviate unnecessary therapy and potentially unveil the diagnosis of paraproteinemia especially related to multiple myeloma.

Bile cast nephropathy in a patient with cholangiocarcinoma - a case report.

Bile cast nephropathy is characterized by the presence of bile casts associated with renal failure and/or proximal tubulopathy in cases of severe hyperbilirubinemia. The clinician should carefully examine the urine samples for characteristic bile-stained granular casts in suspected case.

Clinical and pathological characteristics of non-diabetic renal disease in type 2 diabetes patients.

BACKGROUND: Renal involvement in type 2 diabetes is mainly due to diabetic nephropathy (DN). Nevertheless, a sizable proportion of diabetic patients could actually have nondiabetic renal diseases (NDRDs) or DN plus NDRDs. This study aimed to explore the pathological features of NDRD in diabetic patients and to assess the predictability of diagnosing NDRD (±DN) versus isolated DN on the basis of clinical parameters. METHODS: Medical records of type 2 diabetes patients who underwent renal biopsy under suspicion of NDRD from January 2011 through November 2015 were analyzed retrospectively. RESULTS: A total of 101 patients were enrolled in this study. The most frequent indication for renal biopsy was recent onset of nephrotic syndrome (41%), followed by rapidly progressive renal failure (29%) and active urinary sediment (21%). On renal biopsy, 51% of patients had isolated DN, 20% had isolated NDRD and 29% had DN plus NDRD. IgA nephropathy was the most common cause of isolated NDRD, whereas acute tubular necrosis (39%) and acute interstitial nephritis (33%) were the main causes of NDRD superimposed on DN. Male gender, short-duration diabetes (<8 years), lower glycated hemoglobin and active urinary sediment (≥10 red and white blood cells per high-power field) were independent predictors of NDRD according to multiple logistic regression analysis. CONCLUSIONS: Judicious use of renal biopsy revealed NDRD (±DN) in nearly half of type 2 diabetes patients with atypical renal presentation, especially in male patients with well-controlled diabetes, those who have had diabetes for a short duration and those with active urinary sediment.

The Impact of Macro-and Micronutrients on Predicting Outcomes of Critically Ill Patients Requiring Continuous Renal Replacement Therapy.

Critically ill patients with acute kidney injury (AKI) who receive renal replacement therapy (RRT) have very high mortality rate. During RRT, there are markedly loss of macro- and micronutrients which may cause malnutrition and result in impaired renal recovery and patient survival. We aimed to examine the predictive role of macro- and micronutrients on survival and renal outcomes in critically ill patients undergoing continuous RRT (CRRT). This prospective observational study enrolled critically ill patients requiring CRRT at Intensive Care Unit of King Chulalongkorn Memorial Hospital from November 2012 until November 2013. The serum, urine, and effluent fluid were serially collected on the first three days to calculate protein metabolism including dietary protein intake (DPI), nitrogen balance, and normalized protein catabolic rate (nPCR). Serum zinc, selenium, and copper were measured for micronutrients analysis on the first three days of CRRT. Survivor was defined as being alive on day 28 after initiation of CRRT.Dialysis status on day 28 was also determined. Of the 70 critically ill patients requiring CRRT, 27 patients (37.5%) survived on day 28. The DPI and serum albumin of survivors were significantly higher than non-survivors (0.8± 0.2 vs 0.5 ±0.3g/kg/day, p = 0.001, and 3.2±0.5 vs 2.9±0.5 g/dL, p = 0.03, respectively) while other markers were comparable. The DPI alone predicted patient survival with area under the curve (AUC) of 0.69. A combined clinical model predicted survival with AUC of 0.78. When adjusted for differences in albumin level, clinical severity score (APACHEII and SOFA score), and serum creatinine at initiation of CRRT, DPI still independently predicted survival (odds ratio 4.62, p = 0.009). The serum levels of micronutrients in both groups were comparable and unaltered following CRRT. Regarding renal outcome, patients in the dialysis independent group had higher serum albumin levels than the dialysis dependent group, p = 0.01. In conclusion, in critically ill patients requiring CRRT, DPI is a good predictor of patient survival while serum albumin is a good prognosticator of renal outcome.