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Dear editor: Colonoscopy is critically dependent on adequate pre-procedural bowel cleansing and oral sodium phosphate bowel purgati-ves (OSP) have been used with good acceptance and efficacy for this purpose 1. Among others metabolic and clinical disturbances described after the procedure, acute kidney injury may be a serious complication 2,3. We p...
Citations
... Elimination of phosphate through kidney mainly depends on the renal threshold and the ltered load. Elevated levels of phosphate in plasma or renal tubules could lead to calcium-phosphate crystal deposition which bind to the tubular epithelial cells resulting in reactive oxygen damage [32,33]. Some suggest that it is the main pathway inducing renal impairment [32,34]. ...
Background The incidence of acute kidney injury(AKI) is high in critically ill patients with rhabdomyolysis. Limited evidence was proved of the association between serum phosphate levels at intensive care unit(ICU) admission and the subsequent risk of AKI. Our study aims to assess if serum phosphate level at admission was independently associated with AKI risk in these patients.
Methods This study extracted and analyzed data from Medical Information Mart for Intensive Care-Ⅲ(MIMIC-Ⅲ,version1.4). Rhabdomyolysis was defined as a peak creatine kinase(CK) level higher than 1000 U/L. Serum phosphate was measured within the first day into the ICU and was categorized to 4 groups(<2.6, 2.6-3.4, 3.5-4.5, >4.5mg/dl). AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. Adjusted smoothing spline plots and multivariate logistic regressions were carried out to explode the association between serum phosphate and risk of AKI. Subgroup analyse was applied to verify the consistency of the association.
Results Three hundred and twenty-one patients(67.8% male) diagnosed as rhabdomyolysis were eligible for this analysis. AKI occurred in 204(63.6%) patients of total. Incidence of AKI with admission serum phosphate groups<2.6, 2.6-3.4, 3.5-4.5 and>4.5mg/dl were 52.6%, 56.8%, 68.4% and 75.9%, respectively. Smoothing spline curve showed that there was a positive curve between the elevated phosphate values and increasing risk of AKI, and there was no threshold saturation effect. In multivariate logistic regression, OR was 1.3(95%CI 1.1-1.6, P=0.012, P trend=0.034) after adjusting confounders. Subgroup analyses proved the consistency of the relationship in these patients except in the strata of creatine kinase.
Conclusion In rhabdomyolysis patients admitted to ICU, serum phosphate level at admission was independently associated with an increased risk of AKI. As phosphate levels rise, the risk of AKI increased.
... 5,6 Although seen particularly in patients with decreased urinary phosphate excretion, hyperphosphatemia can also be caused by excessive phosphate administration especially phosphatecontaining laxative. [7][8][9] Most hyperphosphatemic patients are usually asymptomatic though the clinical manifestations depend on the severity and onset of hyperphosphatemia. Patients with acute hyperphosphatemia typically present with signs and symptoms of hypocalcemia, such as perioral numbness, tetany, and seizure, whereas chronic hyperphosphatemia generally lead to the deposition of phosphate and calcium in soft tissues, resulting in vascular calcification and tumoral calcinosis in patients with chronic kidney disease. ...
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. 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.
... Publications were identified by a systematic literature search in which nineteen case of acutely severely impaired renal function are described after administration of phosphate as a treatment for bowel cleansing in preparation for colonoscopy (Fine and Patterson, 1997;Vukasin et al., 1997;Orias et al., 1999;Markowitz et al., 2004;Gonlusen et al., 2006;Santos et al., 2010;Cakar et al., 2012;Arikan et al., 2013). ...
Abstract The Panel on Food Additives and Flavourings added to Food (FAF) provided a scientific opinion re‐evaluating the safety of phosphates (E 338–341, E 343, E 450–452) as food additives. The Panel considered that adequate exposure and toxicity data were available. Phosphates are authorised food additives in the EU in accordance with Annex II and III to Regulation (EC) No 1333/2008. Exposure to phosphates from the whole diet was estimated using mainly analytical data. The values ranged from 251 mg P/person per day in infants to 1,625 mg P/person per day for adults, and the high exposure (95th percentile) from 331 mg P/person per day in infants to 2,728 mg P/person per day for adults. Phosphate is essential for all living organisms, is absorbed at 80–90% as free orthophosphate excreted via the kidney. The Panel considered phosphates to be of low acute oral toxicity and there is no concern with respect to genotoxicity and carcinogenicity. No effects were reported in developmental toxicity studies. The Panel derived a group acceptable daily intake (ADI) for phosphates expressed as phosphorus of 40 mg/kg body weight (bw) per day and concluded that this ADI is protective for the human population. The Panel noted that in the estimated exposure scenario based on analytical data exposure estimates exceeded the proposed ADI for infants, toddlers and other children at the mean level, and for infants, toddlers, children and adolescents at the 95th percentile. The Panel also noted that phosphates exposure by food supplements exceeds the proposed ADI. The Panel concluded that the available data did not give rise to safety concerns in infants below 16 weeks of age consuming formula and food for medical purposes.
... As CaP levels increase, precipitation of calcium phosphate crystals may occur [22,23]. Acute phosphate nephropathy has not only been described after phosphate containing bowel preparation [37][38][39], but also been reported in patients who received oral or intravenous phosphate replacement [40,41]. Elevated serum calcium levels are associated with an increase in urinary calcium excretion due to compensatory increase in the filtered load and a decrease in the tubular reabsorption of calcium [42,43]. ...
Background: Increased serum calcium-phosphate product (CaP) can result in acute kidney injury (AKI) due to tubular and interstitial calcium phosphate deposits. CaP of >55 mg²/dL² is also associated with systemic calcification. However, the risk of AKI development among hospitalized patients with different admission calcium-phosphate product levels remains unclear.
Methods: All adult hospitalized patients who had both admission serum calcium and phosphate levels available from 2009 through 2013 were enrolled. Admission CaP was categorized based on its distribution into six groups (<22, 22-<27, 27-<32, 32-<37, 37-<42 and ≥42 mg²/dL²). The odds ratio (OR) of in-hospital mortality by admission CaP, using the CaP category of <22 mg²/dL² as the reference group, was obtained by logistic regression analysis.
Results: After excluding patients with end-stage renal disease, without serum creatinine measurement, and those who presented with AKI at the time of admission, a total of 9,864 patients were studied. In-hospital AKI occurred in 1,478 patients (15.0%). The incidence of AKI among patients with admission CaP <22, 22 to <27, 27 to <32, 32 to <37, 37 to <42, and ≥42 mg²/dL² was 11.1%, 12.4%, 14.9%, 15.2%, 17.5%, and 19.9%, respectively. After adjusting for potential confounders, a CaP ≥37 mg²/dL² was associated with an increased risk of developing AKI with OR of 1.53 (CI 1.19-1.96) and 1.63 (CI 1.25-2.14) in patients with admission CaP 37-<42 and ≥42, respectively. Subgroup analysis based on eGFR consistently demonstrated that CaP ≥37 mg²/dL² was associated with an increased risk of developing AKI in both chronic kidney disease (CKD) and non-CKD patients.
Conclusion: Elevated admission CaP was independently associated with an increased risk for in-hospital AKI.
... Of 5,036 patients, 699 (14%) had CKD. Subgroup analysis to assess the risk of AKI stratified by CKD status was performed (Supplementary Table 5Table [28][29][30]. Hyperphosphatemia is also seen in rhabdomyolysis [31], when phosphate is released from damaged muscle cells [32]. The release of myoglobin and phosphate can subsequently cause AKI via tubular injuries [31,32]. ...
... 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 There are several plausible explanations for the association between increased AKI risk and elevated phosphate levels. Previous reports of phosphate administration during bowel preparation have demonstrated that elevated phosphate levels can lead to AKI due to phosphate nephropathy [28][29][30]. Elevated phosphate levels in the plasma or tubular compartments can result in deposition of calcium phosphate crystals in renal tubules causing AKI [17-20, [28][29][30]. Hyperphosphatemia is also seen in rhabdomyolysis [31], when phosphate is released from damaged muscle cells [32]. ...
... Previous reports of phosphate administration during bowel preparation have demonstrated that elevated phosphate levels can lead to AKI due to phosphate nephropathy [28][29][30]. Elevated phosphate levels in the plasma or tubular compartments can result in deposition of calcium phosphate crystals in renal tubules causing AKI [17-20, [28][29][30]. Hyperphosphatemia is also seen in rhabdomyolysis [31], when phosphate is released from damaged muscle cells [32]. The release of myoglobin and phosphate can subsequently cause AKI via tubular injuries [31,32]. ...
Background:
Evidence on the association between elevated admission serum phosphate and risk of in-hospital acute kidney injury (AKI) is limited. The aim of this study was to assess the risk of AKI in hospitalized patients stratified by admission serum phosphate level.
Methods:
This is a single-center retrospective study conducted at a tertiary referral hospital. All hospitalized adult patients who had admission phosphate measurement available between January and December 2013 were enrolled. Admission phosphate was categorized into 6 groups (< 2.4, 2.4-2.9, 2.9-3.4, 3.4-3.9, 3.9-4.4, and ≥ 4.4 mg/dl). The primary outcome was in-hospital AKI occurring after hospital admission. Logistic regression analysis was performed to obtain the odds ratio of AKI for various admission phosphate strata using the phosphate 2.4-2.9 mg/dl level (lowest incidence of AKI) as the reference group.
Results:
After excluding patients with end-stage renal disease (ESRD), without serum phosphate measurement, and those with AKI at time of admission, a total of 5036 patients were studied. Phosphate levels of < 2.4 and ≥ 4.4 mg/dl were found in 458 (9.1%) and 585 (11.6%) patients, respectively. In-hospital AKI occurred in 595 (11.8%) patients. The incidence of AKI among patients with admission phosphate < 2.4, 2.4-2.9, 2.9-3.4, 3.4-3.9, 3.9-4.4, and ≥ 4.4 mg/dl was 10.5, 9.5, 11.8, 10.0, 12.8, and 17.9%, respectively. After adjusting for potential confounders, admission serum phosphate > 4.4 mg/dl was associated with an increased risk of developing AKI with an odds ratio of 1.72 (95% confidence interval 1.20-2.47), whereas admission serum phosphate levels < 4.4 mg/dl were not associated with development of AKI during hospitalization.
Conclusion:
Elevated admission phosphate is associated with an increased risk for in-hospital AKI.
... Biopsy-confirmed APhN has been described in a number of patients with preexisting CKD [50,88,89,112,118,121,122]. Moreover in population studies, chronic renal insufficiency has been identified as a significant risk factor for AKI after OSP use [99,123]. ...
... The incidence of clinically important adverse renal events after OSP use cannot be exactly quantified in the general or at-risk populations, since the majority of significant problems are drawn from relatively few (» 20) isolated case reports or case series of biopsy-confirmed APhN [7,50,52,67,80,[87][88][89][90]95,109,[111][112][113][114][115][116][117][118]121,122,124,128,129]. ...
Sodium phosphate purgatives are used for bowel preparation before endoscopic or radiologic examination and occasionally for treatment of severe obstipation. Generally, they are well tolerated and effective; however, safety concerns exist regarding serious renal injury and electrolyte disturbances after administration of these drugs.
The review presents complications associated with the use of agents containing sodium phosphate with regard to electrolyte disorders and renal impairment, namely acute phosphate nephropathy (APhN). This paper discusses the pathophysiology, histopathological findings, clinical symptoms, diagnosis and treatment of APhN. Additionally, it examines the epidemiology of adverse renal events and the safety of using sodium phosphate preparations prior to colonoscopy.
Because of safety concerns, sodium phosphate purgatives are not recommended for routine bowel cleansing. Despite some serious and even fatal adverse events associated with these drugs when used with at-risk patients, available data suggest that administration of sodium phosphate purgatives is relatively safe in nonrisk individuals(i.e., in adequately hydrated, otherwise healthy adults, younger than 55 years with evidence of normal renal function).
Background
The incidence of acute kidney injury (AKI) is high in critically ill patients with rhabdomyolysis. Limited evidence was proved of the association between serum phosphate levels at intensive care unit (ICU) admission and the subsequent risk of AKI. Our study aims to assess if serum phosphate levels at admission were independently associated with AKI risk in these patients.
Methods
This study extracted and analyzed data from Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ, version1.4). Rhabdomyolysis was defined as a peak creatine kinase(CK) level higher than 1000 U/L. Serum phosphate was measured within the first day into the ICU and was categorized to 4 groups(<2.6, 2.6-3.4, 3.5-4.5, >4.5mg/dl). AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. Adjusted smoothing spline plots and multivariable logistic regressions were carried out to explode the association between serum phosphate and risk of AKI. Subgroup analyse was applied to verify the consistency of the association.
Results
Three hundred and twenty-one patients (68% male) diagnosed as rhabdomyolysis were eligible for this analysis. AKI occurred in 204(64%) patients of total. Incidence of AKI with admission serum phosphate groups<2.6, 2.6-3.4, 3.5-4.5 and>4.5mg/dl were 53%, 57%, 68% and 76%, respectively. Smoothing spline curve showed that there was a positive curve between the elevated phosphate values and increasing risk of AKI, and there was no threshold saturation effect. In multivariable logistic regression, OR was 1.2(95%CI 1.0-1.5, P=0.035, P trend=0.041) after adjusting confounders. Subgroup analyses proved the consistency of the relationship in these patients, possibly, except in the strata of potassium.
Conclusion
In rhabdomyolysis patients admitted to ICU, serum phosphate levels at admission were independently associated with an increased risk of AKI. As phosphate levels rise, the risk of AKI increased.
