Fractional Excretion Of Magnesium Research Articles

Utility of fractional excretion of magnesium in diagnosing renal magnesium wasting in pediatric nephrology practice

BackgroundFractional excretion of magnesium (FEMg) is commonly used to diagnose of renal magnesium (Mg) wasting, but it can be affected by serum Mg (SMg) and serum creatinine concentration (SCr). We investigated the sensitivity and specificity of FEMg to diagnose Mg wasting in subgroups with different SMg and eGFR (estimated glomerular filtration rate) in pediatric nephrology practice. MethodsOne hundred and nineteen patients (59 males and 60 females, median 15 years) seen in our pediatric clinic were investigated for FEMg, SMg, eGFR, and urine Mg-to-creatinine ratio (Mg/Cr). Normal eGFR was defined as ≥ 90 ml/min/1.73 m2 or for infants SCr < chronic kidney disease stage 2. Urine Mg/Cr was compared with age-specific reference values. ResultsSixteen of all patients (13 %) had hypomagnesemia. All had FEMg greater than the cut-off value of 2 %. Only 4 patients had elevated urine Mg/Cr. Of 65 patients with normal SMg and eGFR, 19 had FEMg above the cut-off value of 4 %. Of these, 13 patients had elevated urine Mg/Cr i.e. Mg wasting (sensitivity and specificity of FEMg, 93 % and 88 %, respectively). Among 38 patients with normal SMg and low eGFR, 30 had FEMg > 4 %, but only 6 had elevated urine Mg/Cr (sensitivity 100 % and specificity 25 %). Overall, hypomagnesemic patients and normomagnesemic patients with elevated urine Mg/Cr were diagnosed with Mg wasting (36/119, 30 %). ConclusionsFEMg has variable sensitivity and specificity depending on SMg and eGFR in the diagnosis of Mg wasting. Mg wasting is not uncommon in pediatric nephrology practice.

Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure: tacrolimus versus voclosporin.

Calcineurin inhibitors affect kidney electrolyte handling and blood pressure through an effect on the distal tubule. The second generation calcineurin inhibitor voclosporin causes hypomagnesemia and hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally. Rats were treated with voclosporin, tacrolimus or vehicle for 28 days. Dosing was based on a pilot experiment to achieve clinically therapeutic concentrations. Drug effects were assessed by electrolyte handling at day 18 and 28, thiazide testing at day 20, telemetric blood pressure recordings, and analysis of mRNA and protein levels of distal tubular transporters at day 28. Compared to vehicle, tacrolimus but not voclosporin significantly increased the fractional excretions of calcium (>4-fold), magnesium and chloride (both 1.5-fold) and caused hypomagnesemia. Tacrolimus but not voclosporin significantly reduced distal tubular transporters at mRNA and/or protein level, including the sodium-chloride cotransporter, transient receptor melastatin 6, transient receptor potential vanilloid 5, cyclin M2, sodium-calcium exchanger and calbindin-D28K. Tacrolimus but not voclosporin reduced the mRNA level and urinary excretion of epidermal growth factor. The saluretic response to hydrochlorothiazide at day 20 was similar in the voclosporin and vehicle groups, whereas it was lower in the tacrolimus group. The phosphorylated form of the sodium-chloride cotransporter was significantly higher at day 28 in rats treated with voclosporin than in those treated with tacrolimus. Tacrolimus transiently increased blood pressure, whereas voclosporin caused a gradual but persistent increase in blood pressure which was further characterized by high renin, normal aldosterone, and low endothelin-1. In contrast to tacrolimus, voclosporin does not cause hypercalciuria and hypomagnesemia, but similarly causes hypertension. Our data reveal differences between the distal tubular effects of tacrolimus and voclosporin and provide a pathophysiological basis for the clinically observed differences between the two calcineurin inhibitors.

A Comparative Analysis of Fractional Excretion of Sodium, Potassium and Magnesium among T2DM Patients with Increased Albuminuria and Normal Albuminuria in a Tertiary Care Hospital- An Observational Study

Background: T2DM often leads to diabetic kidney disease, a condition marked by change in GFR and urinary albumin excretion. The renal handling of key electrolytes like sodium, potassium, and magnesium plays a crucial role in the progression of renal tubulointerstitial damage in diabetic patients. Aim of the study: The aim of this study was to compare the fractional excretion of sodium, potassium and magnesium among T2DM patients with increased albuminuria and normal albuminuria. Methods: This observational study was conducted in Department of Nephrology, Chattogram, Bangladesh from February 2021 to January 2022. Total 125 patients with T2DM were included in this study. Result: Baseline characteristics showed no significant differences across the study groups. Biochemically, eGFR decreased non-significantly from 95.5 to 86.1 ml/min/1.73 m² across groups, while UACR significantly increased from 14.3 to 1056 mg/gm (P&lt;0.001). FBG levels were similar, but 2hPPBG showed a significant decrease from 8.2 to 7.4 mmol/l (P=0.0041). HbA1C levels varied slightly. FENa, FEK, and FEMg showed significant differences across groups, with FENa ranging from 0.59% to 0.56% (P=0.0016), FEK from 9.4% to 6.9% (P=0.0358), and FEMg from 2.87% to 5.58% (P=0.001). Correlations revealed significant negative associations of eGFR with FENa, FEK, and FEMg, and a significant positive correlation of FEMg with UACR. No significant correlations were found between FBG, 2hPPBG, HbA1C, and the electrolytes excretion. Conclusion: Significant variations in the fractional excretion of sodium, potassium, and magnesium were observed. Higher eGFR was associated with lower electrolyte excretion, and a significant positive correlation was found between magnesium excretion and UACR.

SAT219 Severe Isolated Hypocalcemia With Cetuximab &amp; Irinotecan Chemotherapy

Abstract Disclosure: M. Thomas: None. N. Janakiram: None. J. Leary: None. K.E. Foster-Schubert: None. R.R. Narla: None. Background: Electrolyte disorders are commonly seen with chemotherapy (CTX) agents. Cetuximab is an epidermal growth factor receptor inhibitor and irinotecan is topoisomerase 1 inhibitor. Both agents have been associated with hypomagnesemia which can adversely lead to hypocalcemia (HC). Case: A 66-year-old woman with osteoporosis (last bisphosphonate use was 24 months ago), primary hyperparathyroidism status post parathyroidectomy in 2015 (R inferior and superior glands) and 2017 (L inferior gland) with recent diagnosis of metastatic adenocarcinoma of unknown primary who presented with nausea, tetany, leg cramps and found to have severe HC of corrected calcium (CCa) of 5.7, a week post-chemotherapy. On the day of her CTX, her CCa was 7.0, ionized calcium (iCal) of 1.7 with Magnesium (Mg) of 2.0; she received IV calcium (Ca), then underwent CTX. She was prescribed Ca supplements and reports adherence. She returned endorsing the above symptoms with positive Chvostek and Trousseau sign on exam. Labs were notable for CCa of 5.7, iCal of 1.6, Mg of 1.6, Phosphorus of 4.5, PTH 123 (ULN 65), 25-OH vitamin D of 28.6 and normal eGFR. She was hospitalized and received multiple infusions of IV Ca and CCa improved to 7.5. She was discharged on Ca carbonate 1000 mg TID, Mg oxide 420 mg BID and Vitamin D. Before her second cycle of CTX with same agents, she received IV Ca for CCa of 7.3. She remained on Ca and Mg supplements. One week later, she endorsed paresthesia, diarrhea and was admitted again for HC. She was initiated on calcitriol on this admission and 24-hour urine studies showed low Ca excretion and elevated fractional excretion of magnesium (FeMg). Her CCa was 8.0 and she was discharged on calcitriol 0.25 mg BID. Oncology discontinued this CTX regimen. Her HC resolved and calcitriol and Ca supplements were gradually weaned off. Discussion: After both rounds of cetuximab and irinotecan, our patient developed profound HC without hypomagnesemia. Cetuximab can cause occasional Mg wasting syndrome with inappropriate urinary excretion. However, she was started on Mg since her first hospitalization despite normal serum Mg levels. Interestingly, her 24-hour urine studies revealed FeMg of 6.5% suggestive of renal Mg wasting. In the literature, there is a case report of severe HC with irinotecan but they had speculated germline mutations in Ca metabolism genes. It remains unclear how these CTX agents impact Ca homeostasis. It is difficult to discern if the severe HC in our patient could be attributed to Mg wasting with normal Mg levels. It is evident that her HC was associated with the timing of her CTX regimen. Therapy for HC can be complex, involves short- and long-term interventions, and correction is critical. Serum Ca surveillance before and during CTX management of cancer patients may reveal more instances and provide insight into the exact mechanisms. Presentation: Saturday, June 17, 2023

#4394TACROLIMUS BUT NOT VOCLOSPORIN INHIBITS KIDNEY TUBULAR CALCIUM AND MAGNESIUM REABSORPTION IN RATS AT CLINICALLY THERAPEUTIC DOSES

Abstract Background and Aims Clinically, the calcineurin inhibitor tacrolimus frequently causes hypercalciuria and hypomagnesemia by inhibiting kidney tubular calcium and magnesium reabsorption. Voclosporin, a novel calcineurin inhibitor approved in the USA and Europe for the treatment of adults with active lupus nephritis, has fewer side-effects including less hypomagnesemia. However, the differences between the kidney tubular effects of tacrolimus and voclosporin are unknown. To address this, we compared the effects of tacrolimus, voclosporin, and vehicle in rats. Method Tacrolimus (0.5 mg/kg) and voclosporin (0.5 mg/kg) were administrated by daily intraperitoneal injections in male Wistar rats and were compared against vehicle (Cremophor EL: 95% ethanol:saline (5:5:90, v:v:v)) for 28 days (n = 8–9/group). Dosages were determined based on pharmacokinetic studies in rats and aimed to achieve the area under the concentration-time curve observed in clinical studies. At day 18, blood and 24 h urine were collected to measure trough levels of the drugs and to analyze the fractional excretions of calcium and magnesium. At sacrifice, kidneys were harvested for immunoblotting of tubular proteins. Results Both tacrolimus and voclosporin reached clinically therapeutic doses with trough levels of 2.4 μg/L ± 0.6 μg/L and 25.8 μg/L ± 9.6 μg/L, respectively. Compared to vehicle, tacrolimus caused significantly higher fractional excretions of calcium (+348% ± 127%, P &amp;lt; 0.001) and magnesium (+60% ± 38%, P &amp;lt; 0.01) and also caused hypomagnesemia (plasma magnesium 0.65 mmol/L ± 0.04 mmol/L vs. 0.81 mmol/L ± 0.02 mmol/L, P &amp;lt; 0.001). Compared to vehicle, voclosporin only caused a slight, but non-statistically significant, increase in fractional calcium excretion (+ 44% ± 38%, P = 0.08) and did not cause higher fractional magnesium excretion (+5% ± 30%, P = 0.96) or hypomagnesemia (plasma magnesium 0.8 mmol/L ± 0.04 mmol/L, P = 0.9). Compared to vehicle, tacrolimus caused an 11-fold decrease in the protein abundance of the cytosolic calcium-binding protein calbindin-D28K and a 2-fold decrease in the abundance of the sodium-chloride cotransporter (NCC). In contrast, voclosporin did not decrease the protein abundances of calbindin-D28K and NCC. No differences were observed between vehicle, tacrolimus, and voclosporin in the calcium channel TRPV5 and magnesium channel TRPM6 (Figure 1). Conclusion In contrast to the calcineurin inhibitor tacrolimus, voclosporin does not inhibit the kidney tubular reabsorption of calcium and magnesium and therefore does not cause hypercalciuria or hypomagnesemia. A possible explanation for this difference is that tacrolimus but not voclosporin affects tubular transport in the distal convoluted tubule, which was further supported by the selective inhibition of calbindin-D28K and NCC by tacrolimus. Our data show that tubulotoxicity of tacrolimus is not apparent with voclosporin treatment, at clinically relevant doses.

Abstract #1408162: Comparison of Different Doses of Sodium-Glucose Ttransporter-2 Inhibitors (SGLT2i) to SGLT2i with Magnesium Infusions for Refractory Hypomagnesaemia in a Patient with Monogenic Diabetes Type-5 (MODY-5)

MODY-5 is a rare autosomal dominant form of monogenic diabetes attributed to deletions of chromosome 17q12 with impaired expression of HNF1β (Hepatocyte Nuclear Factor 1 homeobox Beta. The deficient HNF1B down regulated the expression of FXYD2. Refractory hypomagnesemia is commonly observed in patients with MODY-5 due to downregulated FXYD2 which blocked the encoding of the γ (gamma) subunit of the Na+-K+-ATPase and indirectly led to hypomagnesemia. SGLT2i have been associated with small but significant increases in serum magnesium (sMg) levels in patients with diabetes. We report our patient's experience comparing the use of SGLT2i at different doses to SGLT2i with Mg infusions for refractory hypomagnesemia in a patient with MODY-5. 29 y/o Caucasian female with family history of young onset diabetes was diagnosed with MODY-5 at the age of 19 years old when she was found to have kidney cysts that were noted incidentally on MRI spine. She presents to our clinic with hypertension, catamenial headaches, hyperuricemia, refractory hypomagnesemia to oral magnesium supplements (400mg twice a day) due to Mg wasting syndrome, congenital pancreatic atresia and exocrine pancreatic insufficiency. sMg levels have been <1.0mg/dl for 2 years and was symptomatic due to it such as fatigue, headaches and muscle aches. Most lately, she could not tolerate more than 1000mg twice a day of oral magnesium due to diarrhea. Prior to starting SGLT2i her sMg was <1.0mg/dl and fractional excretion of magnesium (FEMg) was 14.5% (normal FEMg <4% in the setting of hypomagnesemia). She was started on canagliflozin 100mg and was titrated to 300mg; which has improved her sMg level from 0.9 mg/dl to 1.2mg/dl and was stable with this dose for weeks. FEMg data was not available for the dose change of canagliflozin. She was also started on amiloride 5mg daily. sMg levels have dropped to <1 md/dL when the canagliflozin has been stopped due to insurance but improved again after starting empagliflozin. On 10mg of empagliflozin compared to 25mg of empagliflozin the sMg level has not changed and remained at 1.1mg/dl level but the FEMg improved from 10% to 7.25%. She continued to have symptoms of hypomagnesemia, so she was started on magnesium sulfate 2gm in 100ml normal saline infused over 12hrs 3 times a week for 6 months. Her symptoms improved after the infusion, but they wear off quickly. Magnesium infusions improved the sMg to 1.5mg/dl but the FEMg was 12.6%. Did not improve. Lately due to treatment burden of Magnesium infusion, they were decreased to 2 times per week. SGLT2i improve refractory hypomagnesemia due to Mg wasting syndrome. Her sMg improved to >1 mg/dL with SGLT2i. There was no difference in sMg comparing low versus high doses of empagliflozin, but an improvement in FEMg. Adding magnesium infusion to SGLT2i slightly improved sMg, but at the expense of burden of the disease treatment.

Fibroblast growth factor 23 is independently associated with renal magnesium handling in patients with chronic kidney disease.

Disturbances in magnesium homeostasis are common in patients with chronic kidney disease (CKD) and are associated with increased mortality. The kidney is a key organ in maintaining normal serum magnesium concentrations. To this end, fractional excretion of magnesium (FEMg) increases as renal function declines. Despite recent progress, the hormonal regulation of renal magnesium handling is incompletely understood. Fibroblast Growth Factor 23 (FGF23) is a phosphaturic hormone that has been linked to renal magnesium handling. However, it has not yet been reported whether FGF23 is associated with renal magnesium handling in CKD patients. The associations between plasma FGF23 levels, plasma and urine magnesium concentrations and FEMg was investigated in a cross-sectional cohort of 198 non-dialysis CKD patients undergoing renal biopsy. FGF23 was significantly correlated with FEMg (Pearson's correlation coefficient = 0.37, p<0.001) and urinary magnesium (-0.14, p=0.04), but not with plasma magnesium. The association between FGF23 and FEMg remained significant after adjusting for potential confounders, including estimated glomerular filtration rate (eGFR), parathyroid hormone and 25-hydroxyvitamin D. We report that plasma FGF23 is independently associated with measures of renal magnesium handling in a cohort of non-dialysis CKD patients. A potential causal relationship should be investigated in future studies.

Screening for an Underlying Tubulopathy in Children With Growth Failure, Simply Maths?

BackgroundInvolving pediatric nephrological input in the clinical diagnostic work-up of children with short stature, gave rise to the hypothesis that the presence of an underlying renal tubular disorder in children with short stature is possibly underestimated. This study focussed on the added value of calculated urinary fractional excretion (FE) in the early detection of tubular disorders in children with growth failure.MethodsThis trial was designed as an observational study analyzing the medical files of children between 5 and 16 years who had been referred for short stature to the pediatric endocrinology outpatient clinic at the University Hospital Antwerp between 25/01/2015 and 01/03/2019. Based on the laboratory results of the simultaneously taken blood and urine sample, the fractional excretions of Sodium, Chloride, Potassium, Calcium, Phosphate, and Magnesium were calculated.ResultsOf the 299 patients, 54 patients had at least one deviating fractional excretion value, requiring further investigation (control sample of blood and urine, kidney ultrasound or 24 h urine collection). Genetic screening for tubulopathies was performed in 19 patients. In 5 patients (1.7% of the total population) a tubulopathy was confirmed based on genetic analysis.ConclusionThis study explored the possibility of using fractional excretions as a screening test to obtain an earlier diagnosis of tubular disorders in children with short stature. Of the 299 patients, 5 patients were diagnosed with a genetically confirmed tubulopathy. Based on these results, we propose a flowchart for an additional work-up in all children with a deviating fractional excretion.

Renal Function Assessment by Estimation of Fractional Excretion of Sodium and Magnesium in Asphyxiated Newborn

Background: Fractional excretion of magnesium (FEMg) is found to be the most sensitive index among fractional excretion of solutes to detect tubular damage in glomerulonephritis, although fractional excretion of sodium (FENa) is used to detect renal tubular dysfunction in perinatal asphyxia till date. Aim and Objective: The aim of this article is to assess the diagnostic performance of FENa and FEMg as renal function test in asphyxiated newborns. Materials and Methods: This cross-sectional study was conducted on 100 asphyxiated newborns in Dhaka Shishu (Children) Hospital, Bangladesh, over 1 year. Serum and urine creatinine, sodium, and magnesium were assessed in each patient; FENa and FEMg were calculated. Serum creatinine was regarded as gold standard for renal function. Results: FENa had 63.64% sensitivity, 100% specificity, 100% positive predictive value, 90.70% negative predictive value, and 92% accuracy. FEMg had 100% sensitivity, 66.67% specificity, 45.83% positive predictive value, 100% negative predictive value, and 74% accuracy. Receiver-operating characteristic curve revealed that area under the curve for FENa was 0.990 and for FEMg was 0.833. So, area under the curve for FENa was more than that of FEMg. Conclusion: FENa is better than FEMg in the assessment of renal function of asphyxiated newborns.

LGG-34. Nephrological impact of BRAF inhibitors in a pediatric population of central nervous system tumors: a single institution experience

BRAF inhibitors (iBRAF) are under investigations in ongoing clinical trials for pediatric brain tumor treatment. Preliminary data regarding the pediatric population report pyrexia, hematological, dermatological, cardiac, and ophthalmic toxicities among the most common adverse events. Acute kidney injury (AKI), mainly due to tubular interstitial injury, has been reported in the adult population. With our study we want to contribute to a more comprehensive knowledge of the short- and long-term nephrological adverse effects of iBRAF in a pediatric population. We collected and reviewed clinical and laboratory data of all patients treated with iBRAF for pediatric central nervous system tumors at our Institution and available for publication. AKI was monitored through serial creatinine measurements, kidney function with estimated glomerular filtration rate (eGFR) and kidney injury with creatinuria/proteinuria ratio. Tubular injury was evaluated with fractional excretion of sodium, potassium and magnesium and with glycosuria. Moreover, urine was examined to detect presence and morphology of erythrocytes. Eight patients were identified, 3 females; median age at treatment start was 9 years (range 2,75 – 18,75). Six patients with BRAFV600E–mutated pediatric Low-Grade Glioma were treated with Vemurafenib, 1 patient with BRAFV600E-mutated pediatric High-Grade Glioma was treated with Vemurafenib and 1 patient with BRAFV600E-mutated Langerhans Cell Histiocytoses was treated with Dabrafenib. Seven patients were considered for analysis. After a median follow up of 3,83 years (range 2,25 – 6,58) no AKI was reported and all patients but two retained normal eGFR at last follow up. No tubular and glomerular injury laboratory findings were detected, and erythrocytes in the urine resulted always below the upper limit of normality. CONCLUSIONS: iBRAF were not associated with AKI and tubular injury. Nevertheless, some data, namely significative decrease of eGFR in two out of seven patients, warrants further investigations.

Renal Magnesium Handling: A Comparison Between Dogs With Chronic Kidney Disease and Healthy Elderly Dogs

Chronic kidney disease (CKD) and aging are known to possibly cause a progressive reduction in glomerular filtration rate, which may be associated with an increase in fractional excretion of electrolytes due to an adaptive response of the remaining functioning nephrons. However, the behavior of magnesium excretion has not been studied in CKD and healthy elderly dogs. The objective was to evaluate the fractional excretion of magnesium (FEMg) in dogs with (CKD) compared to healthy elderly dogs. Sixteen healthy elderly dogs and 43 dogs with CKD were divided into 3 groups (CKD 2 [n = 14], CKD 3 [n = 17], CKD 4 [n = 12]), in accordance with the current International Renal Interest Society (IRIS) criteria that were used in this study. Blood samples were obtained by jugular venipuncture and urine samples were obtained by cystocentesis. The FEMg was evaluated at a single time point in both urine and blood samples. FEMg was significantly higher in dogs with CKD compared to healthy elderly dogs, especially in advanced stages. This preliminary study demonstrates that FEMg may be altered in dogs with CKD. Further research is warranted to elucidate magnesium's potential role in cardiovascular and arterial calcification in dogs with CKD as observed in humans with CKD.

Hypomagnesemia in the Cancer Patient.

Hypomagnesemia is a common medical problem that contributes to the morbidity and mortality of patients with cancer. This review summarizes magnesium physiology and highlights the mechanisms underlying magnesium disturbances due to cancer and cancer treatment. The causes of hypomagnesemia can be categorized according to the pathophysiologic mechanism: decreased intake, transcellular shift, gastrointestinal losses, and kidney losses. Patients with cancer are at risk for opportunistic infections, frequently experience cardiovascular complications, and often receive classes of medications that cause or exacerbate hypomagnesemia. Also, cancer-specific therapies are responsible for hypomagnesemia, including platinum-based chemotherapy, anti-EGF receptor mAbs, human EGF receptor-2 target inhibitors (HER2), and calcineurin inhibitors. Urinary indices, such as the fractional excretion of magnesium, can provide useful information about the etiology. The management of hypomagnesemia depends on the magnitude of hypomagnesemia and the underlying cause. We recommended checking serum magnesium at the beginning of treatment and as part of routine monitoring throughout cancer treatment. Opportunities exist for potential research and practice improvement, including further characterization of hypomagnesemia regarding the clinical effect on cancer outcomes, preventing hypomagnesemia in patients receiving high-risk anticancer agents, and developing effective therapeutic strategies.

Deranged Fractional Excretion of Magnesium and Serum Magnesium Levels in Relation to Retrograde Glycaemic Regulation in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes (T2DM) has been associated with deficiencies in serum magnesium level, decreasing insulin sensitivity and glucose metabolism. Glycosylated hemoglobin (Hb1Ac) is a biomarker of glucose values within the half-life of the erythrocyte, that is, 3 months. Low circulating and intracellular magnesium levels can modify glucose metabolism and insulin sensitivity. Renal solute management is a parameter little used to estimate circulating and excreted concentrations of elements such as magnesium. The purpose of this study was to assess and associated fractional excretion of magnesium (FEMg) and serum magnesium with metabolic parameters, especially Hb1Ac percent, in a group of well characterized subjects with T2DM and non-diabetics subjects (ND). According to Hb1Ac, two groups were compared and associated with existing biochemical parameters, included Hb1Ac, fasting glucose, lipid profile, serum creatinine, serum magnesium and urinary creatinine for FEMg. HbA1c levels were explained by serum magnesium in 25%. Serum magnesium levels in the ND group were higher than in the T2DM group and this was a statistically significant difference. Serum magnesium ≤1.8 is a risk factor (OD 16.1; P=0.021) for an HbA1c ≥ 6.5%. In this study, hypomagnesemia was a parameter strongly associated with the diagnosis and progression of T2DM, while FEMg showed no significant association.

Fractional excretion of magnesium as an early indicator of renal tubular damage in normotensive diabetic nephropathy

Abstract Objectives The aim of the present study is to evaluate the diagnostic powers of fractional magnesium, sodium and potassium as markers of renal tubular damage in normotensive type 2 diabetes mellitus (T2DM) patients with respect to microalbuminuria and estimated glomerular filtration rate (eGFR). Materials and methods Forty healthy volunteers and 91 normotensive T2DM patients were included in the study. Patient group was divided into two according to albuminuria level; 49 were normoalbuminuric and 42 were microalbuminuric. In addition to albumin in urine, urine and serum Na, K, Mg and creatinine values were measured to calculate fractional electrolyte excretion rates. Results In normoalbuminuric and microalbuminuric groups, fractional excretion of magnesium (FEMg) values were found to be significantly higher than the control group (p &lt; 0.05). There was a moderate correlation between FEMg and albümin to cratinin ratio (ACR) (Spearman r = 0.3215, p &lt; 0.05). In the ROC analysis for eGFR and FEMg based on microalbuminuria, the areas under the curve were 0.625 and 0.732, respectively (diagnostic sensitivity 59.52% and 66.67%; specificity 70.79% and 77.53%, p &lt; 0.05). Conclusion For renal tubular damage predicted by microalbuminuria, FEMg could be accepted as a candidate biochemical marker with diagnostic and prognostic value.

Renal ultrasonographic shear-wave elastography and urinary procollagen type III amino-terminal propeptide in chronic kidney disease dogs.

Background and Aim:Renal fibrosis is a well-established pathological alteration associated with chronic kidney disease (CKD) in several species and progresses as CKD advances. Although a renal biopsy is the gold standard for determining renal fibrosis, it is an invasive, impractical method for clinical practice. In humans, ultrasonographic shear-wave elastography (SWE), a novel advanced diagnostic imaging tool, can evaluate renal parenchyma stiffness, and urinary procollagen type III amino-terminal propeptide (uPIIINP), a promising renal fibrosis biomarker in humans, has increasingly been use applied to reduce the biopsies. This study compares renal tissue elasticity observed through SWE Young’s modulus (E) values between healthy dogs (HD) and those with CKD.Materials and Methods:The E value acquired by SWE, uPIIINP levels, and renal function were evaluated in 15 CKD dogs and 15 HD.Results:The renal cortical E values were significantly higher than the renal medullary E values in both groups (p<0.001). Renal cortical and medullary E values in CKD dogs were significantly higher than in HD (p<0.01). Cortical E values had greater significant correlations with renal functional parameters than the medullary E values and had a significant positive correlation with concentrations of plasma creatinine (Cr) (p<0.001); blood urea nitrogen (p<0.01); urine protein Cr ratio (p<0.01); and fractional excretions of sodium (p<0.05), potassium (p<0.05), chloride (p<0.05), and magnesium (p<0.001) while they had a negative correlation with urine specific gravity (p<0.05) and urine osmolality to plasma osmolality ratio (p<0.05). The uPIIINP to Cr (uPIIINP/Cr) ratios of CKD dogs were higher than those of HD (p<0.001). Moreover, the uPIIINP/Cr levels presented significant correlations with the renal cortical E values (p<0.01) and also the renal functional parameters.Conclusion:SWE offers a complementary, non-invasive diagnostic imaging tool for evaluating renal tissue stiffness in CKD dogs with renal function deterioration. In addition, uPIIINP levels are associated with renal function and structural changes in dogs. Therefore, the uPIIINP level might be a non-invasive, complementary, and promising biomarker for evaluating renal fibrosis in canine CKD.

MON-331 Hypomagnesemia: A Preventable Electrolyte Disturbance from Epidermal Growth Factor Receptor Inhibitors

Chemotherapy is a part of the treatment regimen for many different types of cancers and plays a foundational role in treating cancers. With an advent of epidermal growth factor (EGFR) inhibitor and its promising results, it has been widely incorporated in cancer treatment regimen. However, this monoclonal antibody has potential adverse drug reactions especially renal tubular toxicity. Since magnesium is one of the electrolytes that is highly regulated by renal tubular cells, hypomagnesemia is a common electrolyte disturbance in cancer patients. However, the cause of hypomagnesemia may be overlooked. Adequate magnesium supplement in a timely manner can prevent the consequences of hypomagnesemia. We report a case of an elderly man with newly diagnosed squamous cell carcinoma of the tongue with persistent hypomagnesemia after initiation of cetuximab. Magnesium supplement prevented severe hypomagnesemia and maintained serum magnesium. A 77-year-old Caucasian man with stage 3 chronic kidney disease was diagnosed with p16+ poorly differentiated invasive squamous cell carcinoma (cT2-3N2Mx) with basaloid features on the base of the tongue and received cetuximab. He developed acute kidney injury with an elevated serum creatinine up to 2 mg/dL from the baseline serum creatinine of 1.5 to 1.7 mg/dL. He had poor oral intake due to oropharyngeal lesions requiring nutritional supplementation via gastrostomy tube and intermittent intravenous 0.9% sodium chloride infusion. Since starting cetuximab, he had intermittent diarrhea and muscle weakness. Magnesium oxide 400 mg oral daily was an since initiation of cetuximab when serum magnesium a to decrease to 1.7 mg/dL. Throughout in timely months of cetuximab therapy, he had persistent borderline hypomagnesemia with a serum magnesium of 1.4 to 2.2 mg/dL despite receiving an increased magnesium oxide of 400 mg twice a day. Fractional excretion of magnesium (FEMg) was 12.2%. After completion of cetuximab therapy, his serum magnesium became normalized and serum creatinine trended down to 1.6 mg/dL. N/A Our patient started having hypomagnesemia since he received cetuximab therapy. Although there are several potential causes of hypomagnesemia including poor oral intake and diarrhea, high FEMg indicates renal magnesium wasting. Muscle weakness can a by persistent hypomagnesemia. Cetuximab, an EGFR inhibitor, causes impaired distal tubular magnesium reabsorption by inhibiting EGFR receptor at the basolateral membrane of the distal renal tubular epithelial cells which lead to inadequate activation of magnesium channel TRPM6, and subsequently renal magnesium loss. With an increase in the prevalence of malignancy, new chemotherapy agents have been incorporated widely in the cancer treatment, especially EFGR inhibitors. Magnesium plays an important role in maintaining normal cell function and hypomagnesemia results in neuromuscular, cardiovascular and metabolic manifestations. Therefore, proactive magnesium supplement can mitigate these serious consequences of hypomagnesemia until the chemotherapy is completed and hypomagnesemia is normalized.

Liquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: A case report

BACKGROUNDLicorice-induced severe hypokalemic rhabdomyolysis is clinically rare. Gitelman syndrome (GS) is the most common inherited renal tubular disease, while diabetes is one of the most prevalent diseases in the world. Recently, some studies have found that GS patients had higher diabetic morbidity. However, the coexistence of these three diseases has yet to be reported.CASE SUMMARYWe report the case of a 62-year-old Chinese man who was admitted with weakness in the extremities, muscle pain, and dark-colored urine. He had consumed liquorice water daily for seven days prior to admission. The laboratory tests revealed a serum potassium level of 1.84 mmol/L, magnesium 0.68 mmol/L, creatinine phosphokinase (CK) 10117 IU/L, and marked hemoglobinuria. Fractional chloride excretion and fractional magnesium excretion were increased. Plasma renin activity and aldosterone concentration were within the normal ranges. Sequence analysis of the SLC12A3 gene revealed that he had compound heterozygous mutations. The diagnosis of liquorice-induced severe hypokalemic rhabdomyolysis with GS and diabetes was thus genetically confirmed. Serum potassium and CK quickly improved with potassium replacement therapy, hydration, and discontinuation of liquorice ingestion. Upon follow-up at 3 mo, the levels of CK, myoglobin, and potassium remained normal, and magnesium was above 0.6 mmol/L.CONCLUSIONThis case emphasizes that liquorice consumption and GS should be considered causes of hypokalemia and that the diabetic status of GS patients should be noted in the clinic.

Epidermal growth factor and its influencing variables in healthy children and adults

Background & objectiveEpidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations.MethodsBoth healthy adults (n = 50) and children (n = 78) were included. Serum and urinary EGF concentrations were measured with ELISA technology.ResultsSerum EGF was inversely correlated with age (r = —0.873; p<0.001) and positively correlated with serum magnesium (r = 0.597; p<0.001). The urinary EGF was also inversely correlated with age (r = -0.855; p<0.001). In adults and children older than 13 years of age, the urinary EGF significantly differed between sexes (p = 0.001). Urinary EGF was positively correlated with serum magnesium (r = 0.583; p<0.001) and creatinine clearance (r = 0.524; p<0.001) and negatively correlated with the fractional excretion of magnesium (r = 0.248; p = 0.014). In a multivariate model, age and serum magnesium remained independently related to serum EGF while age, serum EGF and serum magnesium remained independently related to urinary EGF.ConclusionsThis study provides valuable insights in urinary and serum EGF patterns in healthy subjects. By systematically correcting EGF for body surface, significant correlations with age, gender and magnesium were observed.

Hypomagnesemia presenting as hypertensive urgency and multiple focal seizures in an infant

A fourty eight day old baby boy presented with a history of unprovoked, left sided focal seizures commencing at the age of 21 days of life and had recurrent hospital admissions previously. He was referred to our tertiary care centre for further evaluation. Clinical assessment on the day of presentation in the Emergency Room revealed a GCS of 13/15, without any focal neurological deficits and an anterior fontanelle that was level, but pulsatile. He was also noted to have severe hypertension. Laboratory parameters revealed hypocalcemia, hypomagnesemia and significantly low 25- OH- vitamin D levels with normal complete blood counts, liver and renal functions. Further endocrinology evaluation revealed a normal PTH level with increased fractional excretion of magnesium in urine. Seizure control was achieved with intravenous calcium and magnesium administration along with antiepileptic drugs. Hypertensive urgency needed appropriate management with nifedipine and labetalol initially and blood pressures normalized only after correction of serum magnesium levels. At discharge, all antihypertensive drugs could be tapered and discontinued. This interesting case highlights the issue of hypomagnesemia manifesting as hypertension, even up to levels of a hypertensive urgency in infants and children.

Serum αKlotho as a Predictor of Graft Dysfunction After Kidney Transplantation

ObjectiveTo improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. MethodsPlasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). ResultsThe median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. ConclusionMeasurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.