Fractional Excretion Of Mg Research Articles

Multiple electrolytes imbalances in a patient with inflammatory bowel disease associated with vitamin D deficiency: a case report

BackgroundInflammatory bowel disease involves chronic inflammation and ulceration, primarily Crohn’s disease and ulcerative colitis. The prevalence of inflammatory bowel disease is rising in industrialized countries. We describe the case of a patient with inflammatory bowel disease and multiple electrolyte disturbances that emphasize the link between a vitamin D deficiency and electrolyte imbalances.CaseAn 86‐year‐old Japanese man with severe hypocalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia was referred to the gastroenterology and hepatology department our university hospital for severe diarrhea and abdominal pain. Based on clinical symptoms and biochemical and endoscopic findings, Crohn’s disease, intestinal Behçet’s disease, and intestinal tuberculosis were considered as differential diagnoses, but a final diagnosis was not reached. Prednisolone, azathioprine, and metronidazole were administered, and no apparent electrolyte abnormality was observed at the patient’s admission to our hospital. On the 80th hospital day, marked hypocalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia were noted and prolonged, despite daily supplementation with Ca and inorganic P. At his consultation with our department, we observed decreased fractional excretion of Ca, tubular reabsorption of phosphate, fractional excretion of K, and fractional excretion of Mg, suggesting the depletion of vitamin D and extrarenal wasting of K and Mg. The patient’s serum Ca and inorganic P were quickly elevated in response to treatment with an active form of vitamin D, and his serum levels of K and Mg were restored to the normal range by an intravenous administration of K and Mg. A vitamin D deficiency is not rare in inflammatory bowel disease and is caused primarily by the decreased intestinal absorption of vitamin D. In the management of electrolyte imbalances in patients with inflammatory bowel disease, clinicians must consider the possible development of vitamin D deficiency-related disorders.ConclusionVitamin D deficiency in entero-Behçet’s disease leads to severe hypocalcemia and hypophosphatemia, highlighting the importance of awareness in management.

Hypomagnesemia and its association with calcineurin inhibitor use in renal transplant recipients

Background Hypomagnesemia is a common electrolyte abnormality following kidney transplantation. Increased renal magnesium (Mg) waste has been linked to calcineurin inhibitors. We aimed to assess the prevalence and risk factors of hypomagnesemia and its association with calcineurin inhibitor use in renal transplant recipients. Patients and methods This is a cross-sectional study carried out on renal transplant recipients, who underwent living-related donor kidney transplantation. All participants underwent detailed history taking and complete physical examination. Serum Mg, trough level of cyclosporine or tacrolimus, fractional excretion of Mg (FEMg), and 24 h urinary Mg, Ca, Ph, Cl, and protein were measured. Results One hundred patients were screened and 80 patients, with a mean age of 39.65 ± 12.14 years, completed the study. Fifty (62.5%) patients were on tacrolimus, and 26 (32.5%) patients were on cyclosporine. Patients had a median serum Mg of 1.80 mg/dl. Hypomagnesemia (Mg<1.7) was present in 17 (21.3%) patients with a median FEMg of 3.08%. There was significant negative correlation between serum Mg level and trough level of tacrolimus and FEMg with a P value of 0.038 and 0.001, respectively. The results of multivariate analyses showed that tacrolimus trough level (P=0.010) and FEMg (P=0.025) were independently correlated with serum Mg. Hypomagnesemia was significantly higher in tacrolimus-treated patients (30%) compared with only 7.7% in cyclosporine-treated patients (P=0.027). Conclusions Hypomagnesemia is common in renal transplant recipients, especially with tacrolimus use mostly due to increased renal Mg wasting. Increased tacrolimus trough level and increased FEMg were predictors of hypomagnesemia.

Sodium Glucose Co-Transporter2 (SGLT2) Inhibition for Refractory Hypomagnesemia in Monogenic Diabetes Type 5 (MODY 5)

Background: MODY 5 is an infrequently reported form of monogenic diabetes attributed to deletions of chromosome 17q12 with impaired expression of HNF1β (Hepatocyte Nuclear Factor 1 Beta). We report a patient who presented with hyperglycemia and hypomagnesemia with an eventual diagnosis of MODY5 that responded to treatment with the SGLT2 inhibitor (SGLT2i), canagliflozin.Clinical case: A 64-year-old male diagnosed with diabetes at age 60 and treated with glimepiride and metformin (HbA1c 6.1–6.2% without hypoglycemia) presented to establish care. He had a prior history of hypermagnesuric hypomagnesemia (serum Magnesium (Mg) 1.4 ± 0.3 mg/dl with Fractional Excretion of Mg (FEMg) 32 ± 3% [values >3–4% in the setting of normal renal function and hypomagnesemia indicates renal Mg loss]) that developed while taking Triamterene- HCTZ for hypertension, prompting discontinuation. Treatment with oral and intravenous (IV) Magnesium along with Amiloride failed to normalize serum Mg levels. Genetic evaluation revealed 17q12 deletion consistent with a diagnosis of MODY 5. Referral to nephrology resulted in discontinuation of glimepiride and addition of canagliflozin 100 mg titrated to 300 mg daily. Mg levels normalized (serum Mg level 1.9 ± 0.1 mg/dL) within 8 weeks of canagliflozin therapy, allowing discontinuation of IV Mg and patient reported improvement in physical stamina and quality of life. At his 1 year follow up visit, his serum Mg remains stable at 1.8mg/dl with a FEMg of 22 ± 2.5%. His current therapy includes Metformin 2 gm, Canagliflozin 300 mg, Amiloride 10 mg tid, and oral Mg.Discussion: Prior to introduction of the SGLT2i, MODY 5 patients required oral and IV Mg repletion in combination with amiloride to achieve near normal Mg levels. Several clinical trials with SGLT2i demonstrated dose and agent dependent improvement in Mg levels in patients with type 2 diabetes. Proposed explanations include reductions in eGFR, changes in intraluminal electrical potential, and activation of renin angiotensin aldosterone system. Mg replacement results not only in symptomatic improvement, but has also been demonstrated to reduce risk of stroke and all-cause mortality.In summary, SGLT2 inhibitors in patients with MODY 5 can be effective in restoring normal Mg levels, improving quality of life, and reducing all cause mortality.

P0042SPECTRUM OF RENAL INVOLVEMENT IN CHILDREN WITH HNF1B NEPHROPATHY

Abstract Background and Aims Hepatocyte nuclear factor 1 gene (HNF1B) encodes for HNF-1ß, a transcription factor that is expressed early in embryonic development and plays a key role for tissue-specific regulations of gene expression in various organs such as the kidneys, urogenital tract, liver, biliary ducts and pancreas. HNF1B disease (MIM 137920) is recognized to represent an autosomal dominant syndromal disorder comprising variable phenotype with renal and extrarenal manifestations. Renal phenotype in HNF1B nephropathy is highly heterogeneous. The aim of the study was to evaluate the clinical characteristics of renal involvement in children with genetically proven HNF1B nephropathy. Method Five children (2M/3F) from unrelated families with heterozygous HNF1β mutations and kidney disorders were examined. We evaluated serum levels of electrolytes, magnesium (Mg), phosphorus (P), uric acid, acid-base composition; urinary excretion of Ca, P, creatinine (Cr); fractional excretion (FE) of Mg, urate (Ur), Na, K; tubular maximum phosphate reabsorption per GFR (TmP/GFR), and urinary β-2 microglobulin. Molecular genetic analysis was performed using by next generation sequencing. Results Cortical or medullary bilateral renal cysts were detected in all five children with HNF1B nephropathy. Kidney hypoplasia, medullary nephrocalcinosis, and low-grade proteinuria (<0.5 g/m2/d) revealed in 2\5 (40%) of cases. One child had vesicoureteral reflux. All patients with HNF1B nephropathy had normal serum level of uric acid and all electrolytes, including Mg. Increased FE of Mg and urinary excretion of β-2 microglobulin was found in all cases. Increased FE of Ur, Na and K revealed in 4\5 (80%) of subjects. Decreased TmP/GFR had 3\5 (60%) of cases. At the first examination of patients aged 1.0 (IQR: 1.0; 2.0) years all of them already had decreased eGFR to CKD stage 2-3. Conclusion The present study demonstrates that patients with HNF1B-associated disease had wide spectrum of renal involvement. The most prevalent features of HNF1B nephropathy in our children were bilateral renal cysts, defects of proximal tubular function with wasting of electrolytes and progression to CKD stage 2-3 at early age.

Proteinuria-associated renal magnesium wasting leads to hypomagnesemia: a common electrolyte abnormality in chronic kidney disease.

Hypomagnesemia (Hypo-Mg) predicts mortality and chronic kidney disease (CKD) progression. However, in CKD, its prevalence, kidney-intrinsic risk factors, and the effectiveness of oral magnesium (Mg) therapy on serum Mg levels is uncertain. In a cross-sectional study enrolling pre-dialysis outpatients with CKD, the prevalence of electrolyte abnormalities (Mg, sodium, potassium, calcium and phosphorus) was compared. In an open-label randomized controlled trial (RCT), we randomly assigned CKD patients to either the magnesium oxide (MgO) or control arm. The outcome was serum Mg levels at 1 year. In 5126 patients, Hypo-Mg was the most common electrolyte abnormality (14.7%) with similar prevalence across stages of CKD. Positive proteinuria was a risk factor of Hypo-Mg (odds ratio 2.2; 95% confidence interval 1.2-4.0). However, stratifying the analyses by diabetes mellitus (DM), it was not significant in DM (Pinteraction = 0.04). We enrolled 114 patients in the RCT. Baseline analyses showed that higher proteinuria was associated with higher fractional excretion of Mg. This relationship between proteinuria and renal Mg wasting was mediated by urinary tubular markers in mediation analyses. In the MgO arm, higher proteinuria or tubular markers predicted a significantly lower 1-year increase in serum Mg. In patients with a urinary protein-to-creatinine ratio (uPCR) <0.3 g/gCre, serum Mg at 1 year was 2.4 and 2.0 mg/dL in the MgO and control arms, respectively (P < 0.001), with no significant between-group difference in patients whose uPCR was ≥0.3 g/gCre (Pinteraction=0.001). Proteinuria leads to renal Mg wasting through tubular injuries, which explains the high prevalence of Hypo-Mg in CKD.

Clinical significance of fractional magnesium excretion (FEMg) as a predictor of interstitial nephropathy and its correlation with conventional parameters.

Elevated urine Mg excretion and its correlation with histological damage in tubulo-interstitial nephropathy (TIN) were reported. Here we investigated the clinical significance of the fractional excretion of Mg (FEMg) for the prediction of TIN. We enrolled and assessed 94 adult patients with various renal diseases diagnosed principally by renal biopsy. Our stratified analysis based on the value of the conventional TIN parameter N-acetylglucosaminidase (NAG) excretion showed that the high-NAG index group (more than median value of NAG-to-Cr ratio, n=47) demonstrated significantly high FEMg values (p=0.017). A univariate analysis revealed a significant correlation between the FEMg and the NAG index (R=0.60) but not for other parameters. A multivariate regression analysis confirmed the significance of the FEMg as an effective predictor of the NAG index. The FEMg showed a significant correlation with the estimated glomerular filtration rate (eGFR) in the patients with eGFR≤30mL/min. The correlation of FEMg with the NAG index was not observed in the primary glomerulonephritis patients but was apparent in the patients with hypertensive nephrosclerosis or interstitial nephritis. Our findings may indicate that the combination of the FEMg and the NAG index can provide a specific, sensitive assessment for TIN in patients without renal insufficiency.

Retrospective cohort study of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis due to CLDN16 mutations.

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder exhibiting a high risk for progressive chronic kidney disease (CKD). This is a retrospective multicentre study of 25 paediatric cases with FHHNC in Poland. Median age at diagnosis was 4 years and median follow-up time was 4.8 years. All cases of FHHNC carried recessive mutations in CLDN16. The founder mutation in CLDN16, Leu151Phe, was the most frequent cause of FHHNC in Polish patients, with 13 (52%) cases being homozygous and 5 (20%) carrying Leu151Phe allele in compound heterozygosity. All cases showed nephrocalcinosis, increased urinary fractional excretion of magnesium and hypercalciuria. Other disease features included hypomagnesaemia (76%), hyperparathyroidism (76%), hyperuricaemia (56%) and hypocitraturia (60%). Treatment with thiazides effectively reduced hypercalciuria in most cases. During follow-up, renal function declined in 60% of patients; 12% of patients reached CKD stage 3 or 4 and one patient developed end-stage renal failure. We report one of the largest cohorts of FHHNC cases caused by CLDN16 mutations. A missense variant of CLDN16, Leu151Phe, is the most common mutation responsible for FHHNC in Poland. Additionally, we found that normomagnesaemia does not exclude FHHNC and the calculation of fractional excretion of Mg can be diagnostic in the setting of normomagnesaemia. We also demonstrate the efficacy of a treatment with thiazides in terms of hypercalciuria in the majority of patients.

Functional Activities of Mutant Calcium-Sensing Receptors Determine Clinical Presentations in Patients With Autosomal Dominant Hypocalcemia

Autosomal dominant hypocalcemia (ADH) is a congenital isolated hypoparathyroidism caused by activating mutations in the calcium-sensing receptor (CASR) gene. The clinical features of ADH are heterogeneous; some patients are asymptomatic, and others show severe hypocalcemia with Bartter's syndrome. We therefore recruited 12 patients with ADH to clarify the determinants of their clinical presentation. We studied two sporadic and 10 familial cases of ADH. Serum concentrations of calcium, intact PTH, and magnesium (Mg(2+)) were measured in each patient. Fractional excretion of Mg (FE(Mg)) was calculated in spot urine samples. A nuclear factor of activated T cells luciferase assay was used to analyze the responsiveness of each mutant CaSR to extracellular Ca(2+). Genomic analysis revealed five known activating mutations and a novel mutation, E481K, in the CASR. Patients with the A843E, C131W, or F788C mutation showed hypomagnesemia with elevated FE(Mg). Intact PTH in these patients was consistently near the detection limit. In contrast, patients with the P221L, K47N, or E481K mutation exhibited normal Mg(2+) levels. In these patients, intact PTH increased in response to low calcium, and their maximum intact PTH exceeded the lower limit of the reference range. Functional analysis showed an association between the disease severity and the in vitro activity of the mutant CaSR. The functional activity of mutant CaSR determines the serum Mg(2+) level, renal Mg(2+) handling, and intact PTH in patients with ADH. The presence of hypomagnesemia with elevated FE(Mg) may indicate the diagnosis of ADH among patients with PTH-deficient hypoparathyroidism.

An infant with recurrent convulsive seizures of 3 weeks duration: Questions

A 1-month-old Japanese boy was admitted to the hospital with a history of recurrent convulsive seizures of 3 weeks in duration. He was born at term (40 week gestation) at a normal birth weight of 2.76 kg following an uneventful pregnancy. He was the first child of healthy parents; there was no history of consanguinity. The infant was well until the 14th day of life when he developed convulsive seizures. On admission, the physicians observed tetanic manifestations, such as carpopedal spasms and convulsive seizures. The patient’s serum calcium level was 5.0 mg/dL (normal range 8.0–10.5 mg/dL), and the inorganic phosphate level was 6.2 mg/dL (normal range 2.5– 4.5 mg/dL). Calcium gluconate and parathyroid hormone (PTH) were administered intramuscularly in high doses, but the tetanic convulsions did not resolve. At that time, the serum magnesium level was measured and found to be extremely low at 0.16 mEq/L (normal range 1.44–1.81 mEq/L). The urinary excretion of magnesium was also low at 0.13 mEq/day (normal 0.31 mEq/L). Parenteral magnesium therapy (8 mEq/day) was started. After a few days, the serum concentrations of magnesium and calcium increased to nearly normal levels, and the tetanic manifestations disappeared completely. Oral magnesium therapy (magnesium chloride, 1 mEq/kg/day) has been continued without any further tetanic manifestations. The magnesium supplement was discontinued on two occasions, and the tetanic convulsions reappeared promptly. The fractional excretion of Mg for this patient was 2.7 % despite a very low level of serum magnesium (normal range 2.1–14.3 % in normagnesemic individuals, but is close to 0 if there is permanent depletion of magnesium), indicating the presence of a renal magnesium leak. The intestinal absorption of magnesium [(1−Mg in stool/Mg intake)×100 (%)] was lower than the amount of absorption observed in people with normal levels of magnesium (absorption in patient 19.6– 32.9 %; normal levels 50.2–60.2 %). The serum calcium and magnesium levels of the parents were within normal limits.

The TRPM6/EGF Pathway Is Downregulated in a Rat Model of Cisplatin Nephrotoxicity

Cisplatin-induced hypomagnesemia is described in humans and rats, but the underlying mechanisms are still unclear. Recent studies have shown that epidermal growth factor (EGF) stimulates Mg2+ re-absorption in the distal convoluted tubule via the Mg2+ channel TRPM6. This study investigates the role of TRPM Mg2+ channels, claudines, and EGF in the Mg2+ homeostasis in a rat model of cisplatin-induced nephrotoxicity. Wistar rats were given 2.5 mg/kg cisplatin per week for 3 weeks and were euthanized 4 or 9 weeks after the first administration. The cisplatin treatment significantly increased the fractional excretion of Mg2+. Real-time RT-PCR and/or Western blots were performed to assess the renal expression TRPM6, TRPM7, claudin-16, claudin-19, EGF, EGF receptor (EGFR) and EGFR-pathway components. The renal mRNA expression of TRPM6 and EGF showed a significant decrease after cisplatin treatment, while the TRPM7, claudin-16 and EGFR expressions remained stable. The claudin-19 mRNA expression was significantly upregulated after cisplatin treatment. Western blotting confirmed the mRNA expression data for the claudins, but an showed upregulation of EGFR only at week 9. The role of the EGFR pathway, involving Pi3-AKT-Rac1, in cisplatin-induced nephropathy, could not be substantiated in further detail. This study shows that cisplatin treatment results in EGF and TRPM6 downregulation in the rat kidney, causing renal Mg2+ loss. Our results are in line with the hypothesis that EGF influences the renal expression or activation of TRPM6 and plays a significant role in Mg2+ loss in medication-induced nephropathy.

Restoration of renal hemodynamics and functions during black cumin (Nigella sativa) administration in streptozotocin-induced diabetic rats.

BackgroundBlack cumin (Nigella sativa) is an ancient herbal medicine recommended by the World Health Organization. The antioxidant and antihyperglycemic effects of black cumin are well established. Amelioration of renal dysfunction in nephrotoxic rats with black cumin treatment has also been noted. However, the effect of black cumin treatment on renal dysfunction in diabetes mellitus has not been clarified. In this study, the effect of black cumin oil (BC) on changes in renal dysfunction and renal hemodynamics in streptozotocin-induced diabetic rats was evaluated.MethodsThe experiments were performed in male Sprague Dawley rats, divided into four groups (seven in each group): (1) normal rats given tap water (CON); (2) normal rats administered with BC (CON-BC); (3) diabetic rats given tap water only (STZ); and (4) diabetic rats administered with BC (STZ-BC). Diabetes mellitus was induced in the rats by an injection of streptozotocin. BC was given orally at the dose of 1000 mg/kg body weight to the rat in either CON-BC or STZ-BC every day for 8 weeks. Renal hemodynamics and functions in each rat were studied.ResultsRenal hemodynamic changes in STZ-BC rats appeared to increase in terms of glomerular filtration rate, effective renal plasma flow, and effective renal blood flow, while renal vascular resistance and filtration fraction were decreased in comparison with diabetic rats given tap water only (STZ). An improvement of renal tubular dysfunction in STZ-BC rats was indicated by the decreases in fractional excretion of water and Mg++.ConclusionAn administration of BC can restore changes in renal hemodynamics and renal dysfunction in streptozotocin-induced diabetic rats.

Acute-onset hypomagnesemia-induced hypocalcemia caused by the refractoriness of bones and renal tubules to parathyroid hormone

Chronic hypomagnesemia is closely associated with hypocalcemia, which is caused by impaired parathyroid hormone (PTH) secretion or the refractoriness of bone and renal tubules to PTH. The dominant mechanism of acute-onset, hypomagnesemia-induced hypocalcemia is currently unclear. An 83-year-old man who had undergone chemotherapy with carboplatin for prostate cancer suffered from acute diarrhea and finger paresthesia. Laboratory data confirmed hypocalcemia as well as hypomagnesemia. Urinary calcium levels were not measured. However, the urinary fractional excretion of Mg (FE(Mg)) was elevated. Despite elevated PTH levels, the renal tubular maximal reabsorption rate of phosphate to GFR (TmP/GFR) was elevated, and bone formation and resorption markers were suppressed. A magnesium loading test revealed a clear magnesium deficiency. After administration of magnesium, bone marker levels were increased, and TmP/GFR was reduced to normal levels, despite the persistent elevation of PTH. Serum calcium levels eventually increased to approximately the reference range. Clinical histories and these observations both suggest that when patients with hypomagnesemia-induced hypocalcemia rapidly lose magnesium through complications such as diarrhea, the primary cause may be the refractoriness of bone and renal tubules to PTH, rather than impaired PTH secretion.

Effects of the EGFR Inhibitor Erlotinib on Magnesium Handling

A mutation in pro-EGF causes isolated hypomagnesemia, and monoclonal antibodies targeting the extracellular domain of the EGF receptor (EGFR) affect epithelial Mg(2+) transport. The effect of the EGFR tyrosine kinase inhibitor erlotinib on Mg(2+) homeostasis, however, remains unknown. Here, we injected C57BL/6 mice with erlotinib for 23 days and observed a small but significant decrease in serum Mg(2+) concentrations at days 16 and 23, but the fractional excretion of Mg(2+) remained unchanged after 23 days. Semiquantitative immunohistochemical evaluation did not reveal detectable changes in renal expression of transient receptor potential melastatin 6 (TRPM6) protein, the channel that mediates Mg(2+) reabsorption. Patch clamp analysis in TRPM6-expressing cells demonstrated that 30 muM erlotinib inhibited EGF-induced changes in TRPM6 current density and tyrosine phosphorylation of EGFR; 0.3 muM erlotinib did not have these effects. Furthermore, 30 muM erlotinib inhibited EGF-stimulated increases in the mobile fraction of endomembrane TRPM6 channels. In summary, erlotinib can influence Mg(2+) handling but its effect on the systemic Mg(2+) concentration seems less potent than that observed with antibody-based EGFR inhibitors. These data suggest that typical human dosages of erlotinib are unlikely to severely affect serum Mg(2+) concentrations.

Changes in plasma total and ionized magnesium concentrations and factors affecting magnesium concentrations during cardiac surgery.

The purpose of this study was to measure blood total and ionized magnesium concentrations ([TMg] and [Mg(2+)], respectively) and to investigate factors that might be affecting their changes during cardiac surgery using hypothermic cardiopulmonary bypass. Eight patients were examined. All the patients received diuretics and predeposited autologous blood during surgery. No drugs containing Mg(2+) were administered. Nine blood samples and eight urine samples were collected from the pre-induction period to the end of surgery. Hematocrit, [TMg], [Mg(2+)], plasma concentrations of calcium ([Ca(2+)]), creatinine, parathyroid hormone (PTH), urinary concentrations of TMg, and creatinine were measured, and the fractional excretion of Mg (FEMg) was calculated. Both [TMg] and [Mg(2+)] decreased significantly in the prebypass period and remained significantly depressed thereafter. The ionized fraction of magnesium ([Mg(2+)]/[TMg]) was decreased during the postbypass period. Hematocrit decreased significantly from the prebypass period, and FEMg increased significantly after aortic cross-clamping. In conclusion, hemodilution and renal loss were main causes of hypomagnesemia, and citrate in predeposited autologous blood may contribute to the decrease in [Mg(2+)]/[TMg] in the postbypass period. These results suggest that magnesium supplementation under close monitoring of [Mg(2+)] should be required during cardiac surgery.

Effect of a magnesium-deficient diet on serum and urine magnesium concentrations in healthy cats

Abstract Objective To evaluate the efficacy of using serum total and ionized magnesium (Mg) concentrations and urine Mg concentrations to identify Mg deficiency in cats. Animals 6 healthy castrated male cats. Procedure A Mg-replete diet was fed for 37 days, followed by a Mg-deficient diet for 37 days. On days 1, 3, and 7 of the last week of each diet, serum ionized and total Mg concentrations were determined; in addition, urine Mg concentration was determined each day of the last week. Serum total and ionized Mg concentrations were compared with urine Mg concentration, amount of Mg excreted during 24 hours (24-hour urine Mg excretion), ratio of urine Mg concentration to urine creatinine concentration (Umg:Ucr), and urinary fractional excretion of Mg (FEmg) to determine which variable best predicted Mg status. Results Cats fed Mg-deficient diets had significantly lower serum total and ionized Mg concentrations and 24-hour urine Mg excretion values, compared with cats fed Mg-replete diets. Serum total Mg concentration was the best predictor of Mg status. Twenty-four-hour urine Mg excretion was a repeatable, reliable measurement and had the best correlation with serum total Mg concentration. Serum total Mg concentration also correlated with urine Mg concentration, Umg:Ucr, and FEmg. Conclusions and Clinical Relevance Serum total and ionized Mg concentrations can be used to identify cats with dietary-induced Mg deficiencies. Twenty-four-hour urine Mg excretion and urine Mg concentration correlated best with serum total Mg concentration and, therefore, may be the most useful urine variables for identifying Mg deficiency. (Am J Vet Res 1999;60:1159–1163)

SCREENING FOR HYPOMAGNESEMIA IN CYCLOSPORINE OR FK 506 TREATED RENAL TRANSPLANT RECEIPIENTS.

584 Therapy with cyclosporine (CSA) or FK 506 increases the urinary losses of magnesium (Mg) in renal transplant recipients. Hypomagnesemia (hypoMg) has been reported to be associated with hypertension, glucose intolerance, abnormal lipid metabolism and cardiovascular complications. Mg level is often not measured as part of the routine screening blood tests. We have evaluated different variables and the correlation between these variables to detect hypoMg in stable renal transplant recipients. We also evaluated effect of Mg repletion on the variables in hypoMg patients. Of 194 transplant recipients with a s.creatinine <3.0 on either FK 506 or CSA therapy, 14 (7.1%) were found to be hypoMg as defined by s.Mg level <1.6 or ionized Mg <0.90. 14 control patients were also evaluated for different variables of Mg measurement i.e. s.Mg, ion Mg, RBC Mg, Urine Mg (u.Mg) and fractional excretion of Mg (FEr Mg). All 28 patients had s.Mg in range of 1.3 to 2.2 mg/dl (mean 1.71±0.043) s.Mg correlated well with ion Mg (mean 0.97±0.02; R=0.67). Poor correlation was seen between s.Mg and RBC Mg, Urine Mg and FEr Mg. Effects of Mg repletion on these variables at monthly interval are as follows: (Table)TableIn hypoMg patients Mg repletion increases serum and ion Mg but no effect was seen on RBC Mg, U.Mg, FE Mg and ion calcium showed increased trend but did not reach statistical significance. We conclude that serum and ionized Mg values are well correlated and should be used to screen for hypoMg and for Mg therapy in potentially hypoMg renal transplant patients. U.Mg may continue to demonstrate reduced excretion despite of Mg repletion and may not be used as guide for adequate Mg repletion.

Cyclosporine A-induced alterations in magnesium homeostasis in the rat

The immunosuppressive drug cyclosporine A (CsA) exhibits significant nephrotoxicity. Disturbance of magnesium (Mg) homeostasis may be an important component of this nephrotoxicity. It has been suggested that transmigration of Mg from plasma to tissues may be an important component of CsA-induced alterations in Mg homeostasis. In this study, CsA nephrotoxicity in male Wistar rats was investigated and alterations in Mg homeostasis along with other indices of toxicity were assessed. Animals were dosed daily for 14 days I.P. With CsA (20 mg kg body weight). Control animals received vehicle alone. CsA toxicity was evidenced by i) lower gain in body weight, ii) reduced thymus body weight ratio, iii) increased blood urea nitrogen and creatinine, iv) a tendency for reduced plasma magnesium and v) increased urinary Mg excretion and greatly increased fractional excretion of Mg. Tissue Mg analysis did not reveal any changes in thymus or skeletal muscle Mg while Mg in kidney tissue tended to be reduced. Electron microscopy revealed some damage in renal tubules of rats treated with cyclosporine including translucent cytoplasm, vacuolization, rounded and swollen mitochondria, damage to brush border and disruption of basal infoldings. These results indicate that direct renal tubular damage may result from CsA exposure. No evidence was found for CsA-induced movement of Mg from plasma to tissues. CsA-induced altered renal handling of Mg and this renal Mg wasting may be an important consequence of the nephrotoxicity.

Renal magnesium handling in infants and children.

Renal handling of magnesium (Mg) has been incompletely studied during infancy and childhood due to the difficulty, until recently, of measuring the diffusible fraction of plasma Mg. In the present investigation this methodology has been used to assess Mg homeostasis in 45 healthy infants, aged 1 to 12 months, and in 63 healthy children, aged 1 to 15 years. When compared to children, infants had significantly higher plasma values (mean +/- SD) for both total (0.76 +/- 0.08 versus 0.70 +/- 0.06 mmol l-1; p < 0.001) and ultrafilterable Mg (0.51 +/- 0.07 versus 0.49 +/- 0.04 mmol l-1; p < 0.05). No significant correlations were present between values of plasma Mg and plasma concentrations of calcium, creatinine, total protein or albumin. The ratio Umg/Ucr, calculated in the second morning urine (median, 3rd-97th centiles), was also significantly higher during infancy (0.023, 0.009-0.07 versus 0.015, 0.006-0.04; p < 0.001). On the contrary, fractional excretion of Mg (median, 3rd-97th centiles) was identical in both age groups and did not correlate significantly with age (infants: 3.2, 1.0-7.8%, children 3.4, 1.6-8.1%; p = NS). During a Mg infusion, carried out in six children, we could establish an approximative value for renal Mg threshold (plasma ultrafilterable Mg = 0.50 mmol l-1) close to that found in adults. These results indicate that no functional immaturity is present during infancy for renal tubular reabsorption of Mg and that the high Umg/Ucr ratio observed in this age group is a phenomenon not dependent on a higher urinary Mg excretion but probably related to a lower urinary creatinine excretion per unit of lean body mass.

Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans.

The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four-day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a six-day eucapnic recovery period (500 m) under metabolic balance conditions. Chronic respiratory alkalosis (delta PaCO2, -8.4 mm Hg, delta[H+] -3.2 nmol/liter) resulted in a sustained decrement in plasma ionized calcium concentration (delta[IoCa++]p, -0.10 mmol/liter, P less than 0.05) and a sustained increment in plasma phosphate concentration (delta[PO4]p, +0.14 mmol/liter, P less than 0.005) associated with increased fractional excretion of Ca++ (+0.5%, P less than 0.005), decreased phosphate clearance (-6.1 ml/min, P less than 0.025) and decreased excretion of nephrogenous cAMP (-1.5 nmol/100 ml GFR, P less than 0.0025). Urinary phosphate excretion decreased by 15.4 mmol/24 hr on day 1 of chronic respiratory alkalosis (P less than 0.0025), but returned to control values by day 6 despite hyperphosphatemia. Serum intact [PTH] did not change. Sustained hypomagnesuria (-0.8 mmol/24 hr, P less than 0.05) occurred during chronic respiratory alkalosis and was accounted for, at least in part, by decreased fractional excretion of Mg++ (-0.7%, P less than 0.05) in the absence of change in plasma magnesium concentration. Serum 1,25(OH)2D levels were unchanged by chronic respiratory alkalosis. In conclusion, the decrease in nephrogenous cAMP generation despite unchanged serum intact PTH concentration suggests that chronic respiratory alkalosis results in impaired renal responsiveness to PTH as manifested by alterations in PTH-dependent renal calcium and phosphate transport.(ABSTRACT TRUNCATED AT 250 WORDS)