Hypomagnesaemia, an independent risk factor for the development of post-transplant diabetes mellitus in liver and renal transplant recipients? A systematic review.

BACKGROUND: Post-transplantation diabetes mellitus (PTDM) is common after solid organ transplantation. In the past decade, there has been increasing interest in the association between hypomagnesaemia and the development of PTDM. This systematic review aimed to investigate the current knowledge regarding the association between hypomagnesaemia and PTDM in adult liver and renal transplant recipients. METHODS: A literature search of five databases, Medline, Embase, ProQuest, Scopus and Google Scholar, as well as article reference lists, was performed. Eligible studies that focused on adult liver and renal transplant recipients without pretransplantation hyperglycaemia or diabetes were included. Other eligibility criteria included quantitative studies which reported magnesium concentrations, studies with at least 6 months of follow-up, and studies published in English. The Newcastle-Ottawa Assessment Tool was used for the quality assessment. RESULTS: In total, 12 studies were included in the final analysis. Eleven focused on renal transplantation and one on liver transplantation. All studies were medium to high quality with eight out of 12 achieving the highest rating of nine. Eight studies found a negative association between either pretransplant or early post-transplant serum magnesium concentration and the risk of PTDM, three studies found no association between these two variables, and one study found a positive association between the magnesium concentration at 8 weeks after transplantation and glycosylated haemoglobin A1C. CONCLUSIONS: Further large-scale prospective studies with at least 6 months of follow-up are needed to confirm these findings, particularly in liver transplantation, to further clarify and explore the relationship between hypomagnesaemia and PTDM.

Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants.

Variants in the CNNM2 gene are causative for hypomagnesaemia, seizures and intellectual disability, although the phenotypes can be variable. This study aims to understand the genotype-phenotype relationship in affected individuals with CNNM2 variants by phenotypic, functional and structural analysis of new as well as previously reported variants. This results in the identification of seven variants that significantly affect CNNM2-mediated Mg2+ transport. Pathogenicity of these variants is further supported by structural modelling, which predicts CNNM2 structure to be affected by all of them. Strikingly, seizures and intellectual disability are absent in 4 out of 7 cases, indicating these phenotypes are caused either by specific CNNM2 variant only or by additional risk factors. Moreover, in line with sporadic observations from previous reports, CNNM2 variants might be associated with disturbances in parathyroid hormone and Ca2+ homeostasis.

Urinary Acidification Does Not Explain the Absence of Nephrocalcinosis in a Mouse Model of Familial Hypomagnesaemia with Hypercalciuria and Nephrocalcinosis (FHHNC).

Patients with mutations in Cldn16 suffer from familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) which can lead to renal insufficiency. Mice lacking claudin-16 show hypomagnesemia and hypercalciuria, but no nephrocalcinosis. Calcium oxalate and calcium phosphate are the most common insoluble calcium salts that accumulate in the kidney in the case of nephrocalcinosis, however, the formation of these salts is less favored in acidic conditions. Therefore, urine acidification has been suggested to limit the formation of calcium deposits in the kidney. Assuming that urine acidification is causative for the absence of nephrocalcinosis in the claudin-16-deficient mouse model, we aimed to alkalinize the urine of these mice by the ablation of the subunit B1 of the vesicular ATPase in addition to claudin-16. In spite of an increased urinary pH in mice lacking claudin-16 and the B1 subunit, nephrocalcinosis did not develop. Thus, urinary acidification is not the only factor preventing nephrocalcinosis in claudin-16 deficient mice.

Long-term cisplatin nephrotoxicity after childhood cancer: a systematic review and meta-analysis.

BACKGROUND: Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly manifesting as reduced glomerular filtration rate and hypomagnesaemia. Existing literature regarding the epidemiology of long-term nephrotoxicity in childhood cancer describes large variation in prevalence and risk factors. OBJECTIVES: This study is to evaluate the prevalence of, and risk factors for, long-term cisplatin nephrotoxicity after treatment for childhood cancer. STUDY ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they: (i) evaluated participants treated with cisplatin who were diagnosed with cancer < 18 years of age; (ii) investigated any author-defined measure of nephrotoxicity; and (iii) performed this evaluation 3 or more months after cisplatin cessation. Studies whose scope was broader than this were included if appropriate subgroup analysis was performed. RESULTS: Prevalence of reduced glomerular filtration rate (GFR) ranged between 5.9 and 48.1%. Pooled prevalence of reduced GFR using studies with a modern consensus threshold of 90 ml/min/1.73 m2 was 29% (95% CI 0.0-58%). Prevalence of hypomagnesaemia ranged between 8.0 and 71.4%. Pooled prevalence of hypomagnesaemia was 37% (95% CI 22-51%). Substantial heterogeneity was present, with I2 statistics of 94% and 73% for reduced GFR and hypomagnesaemia respectively. All large, long-term follow-up studies described increased risk of reduced GFR with increasing cumulative cisplatin dose. Included studies varied as to whether cisplatin was a risk factor for proteinuria, and whether age was a risk factor for cisplatin nephrotoxicity. LIMITATIONS: A wide range of study methodologies were noted which impeded analysis. No studies yielded data from developing health-care settings. No non-English studies were included, further limiting generalisability. CONCLUSIONS: Both of the most common manifestations of long-term cisplatin nephrotoxicity have a prevalence of approximately a third, with increasing cumulative dose conferring increased risk of nephrotoxicity. Further work is needed to characterise the relationship between reduced GFR and hypomagnesaemia, investigate other risk factors and understand the interindividual variation in susceptibility to nephrotoxicity.

Association of magnesium sulfate use with mortality in critically ill patients with sepsis: a retrospective propensity score-matched cohort study.

BACKGROUND: Trials have demonstrated lower rates of acute kidney injury in critically ill patients receiving magnesium supplementation, but they have yielded conflicting results regarding mortality. METHODS: This is a retrospective cohort study based on the MIMIC-IV (Medical Information Mart in Intensive Care-IV) database. Adult critically ill patients with sepsis were included in the analysis. The exposure was magnesium sulfate use during ICU stay. The primary outcome was 28-day all-cause mortality. Propensity score matching (PSM) was conducted at a 1:1 ratio. Multivariable analyses were used to adjust for confounders. RESULTS: The pre-matched and propensity score-matched cohorts included 10 999 and 6052 patients, respectively. In the PSM analysis, 28-day all-cause mortality rate was 20.2% (611/3026) in the magnesium sulfate use group and 25.0% (757/3026) in the no use group. Magnesium sulfate use was associated with lower 28-day all-cause mortality (hazard ratio [HR], 0.70; 95% CI, 0.61-0.79; P<0.001). Lower mortality was observed regardless of baseline serum magnesium status: for hypomagnesaemia, HR, 0.64; 95% confidence interval (CI), 0.45-0.93; P=0.020; for normomagnesaemia, HR, 0.70; 95% CI, 0.61-0.80; P<0.001. Magnesium sulfate use was also associated with lower ICU mortality (odds ratio [OR], 0.52; 95% CI, 0.42-0.64; P<0.001), lower in-hospital mortality (OR, 0.65; 95% CI, 0.55-0.77; P<0.001), and renal replacement therapy (OR, 0.67; 95% CI, 0.52-0.87; P=0.002). A sensitivity analysis using the entire cohort also demonstrated lower 28-day all-cause mortality (HR, 0.62; 95% CI, 0.56-0.69; P<0.001). CONCLUSIONS: Magnesium sulfate use was associated with lower mortality in critically ill patients with sepsis. Prospective studies are needed to verify this finding.

Clinical features and recovery pattern of secondary hypokalaemic paralysis.

PURPOSE: Information regarding frequency, details of neurological signs and recovery patterns of patients with secondary hypokalaemic paralysis (HP) is limited. This study aimed to analyse the frequency, aetiology, clinical features and recovery patterns of patients with secondary HP. METHODS: The clinical and laboratory records of 18 consecutive patients with secondary HP aged ≥ 18 years admitted to our hospital between April 2011 and March 2022 were reviewed. Patients with inherited hypokalaemic periodic paralysis were excluded. RESULTS: Of the 18 patients, 16 had a common aetiology: chronic alcoholism, diarrhoea or an imbalanced diet. Initial symptoms, such as fatigue, were often atypical. Three patients had prominent asymmetric limb weakness and four had predominant upper limb weakness. On admission, the mean serum potassium and creatine kinase (CK) levels of the patients were 1.90 mmol/L and 4488 U/mL, respectively. Ten patients (56%) had decreased potassium levels after admission, despite potassium replacement treatment (rebound hypokalaemia). Twelve patients presented with increased CK levels even after 2-5 days (delayed hyperCKaemia). Low serum magnesium levels significantly correlated with rebound hypokalaemia. CONCLUSIONS: Secondary HP can be caused by a variety of conditions, but mainly occurs due to lifestyle conditions/disorders. Secondary HP often presents with atypical symptoms, and the initial symptoms can be non-specific. Rebound hypokalaemia and delayed hyperCKaemia are common in secondary HP, despite potassium replacement. As such, careful serial monitoring is needed for patients with secondary HP.

Serum magnesium levels of term neonates with birth asphyxia and relationship to severity of asphyxia.

Background and Aims: Birth asphyxia is one of the three main causes of neonatal mortality in Nigeria. Hypomagnesaemia has been reported amongst severely asphyxiated babies. Despite this, the prevalence of hypomagnesaemia amongst newborns with birth asphyxia has not been well researched in Nigeria. This study set out to determine the prevalence of hypomagnesaemia in term neonates with birth asphyxia and the relationship (if any) between magnesium levels and the severity of birth asphyxia or encephalopathy. Methods: In this cross-sectional analytical study, the serum magnesium levels of consecutive cases of birth asphyxia were compared to that of gestational age-matched healthy term neonates. Babies with Apgar scores <7 in the 5th minute of life were recruited into the study. Blood samples were taken from each baby at birth and 48 h. Serum magnesium was measured using spectrophotometry. Results: Hypomagnesaemia was found in 36 (35.3%) babies with birth asphyxia and 14 (13.7%) healthy controls; this difference was statistically significant (χ2 = 18.098, P = 0.001), with an odds ratio of 3.4 (95% confidence interval = 1.7, 6.9). The median (interquartile range) levels of serum magnesium in babies with mild, moderate and severe asphyxia were 0.7 mmol/L (0.5-1.1), 0.7 mmol/L (0.4-0.9) and 0.7 mmol/L (0.5-1.0), respectively (P = 0.316), while those of babies with mild (stage 1), moderate (stage 2) and severe (stage 3) encephalopathy were 1.2 mmol/L (1.0-1.3), 0.7 mmol/L (0.5-0.8) and 0.8 mmol/L (0.6-1.0), respectively (P = 0.789). Conclusion: This study has shown that hypomagnesaemia was more common in babies with birth asphyxia and there was no relationship between magnesium levels and the severity of asphyxia or encephalopathy.

Evaluation of hypomagnesaemia in diabetic patients with nephropathy in a reference clinical laboratory: A comparative cross sectional study.

Serum Magnesium plays a significant role in different diabetic complications. This comparative cross sectional study was conducted to evaluate serum magnesium levels in patients with Type 2 Diabetes Mellitus (T2DM) with and without nephropathy. A total of 182 diabetic patients (91 with nephropathy and 91 without nephropathy) were included. Odds ratio were calculated and Mann Whitney U test was used to compare quantitative variables; p<0.05 was considered significant. The results showed that 64/91 (70.3%) patients with nephropathy had hypomagnesaemia as compared to 21/91 (23.07%) patients without nephropathy. The risk of hypomagnesaemia was higher in patients with nephropathy than without nephropathy (Odds ratio 2.7 vs 0.34). Median magnesium levels (1.73 mg/dl) were lower in patients with nephropathy as compared to patients without nephropathy (2.09 mg/dl), p<0.01. It is concluded that magnesium levels were significantly lower in patients with diabetic nephropathy as compared to without nephropathy.

The kidney reabsorption-related magnesium depletion score is associated with increased likelihood of abdominal aortic calcification among US adults.

BACKGROUND: Kidney reabsorption plays a vital role in magnesium homeostasis. This study aimed to determine the relationship between the kidney reabsorption-related magnesium depletion score (MDS) and abdominal aortic calcification (AAC). METHODS: We obtained data for 2640 individuals from the National Health and Nutrition Examination Survey database and analysed the relationship between the MDS and AAC score. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. AAC was quantified by the Kauppila score system based on dual-energy X-ray absorptiometry. We performed stratified analysis and multiple equation regression analysis. R and EmpowerStats were used for data analysis. RESULTS: A total of 2640 participants were included with the mean AAC score of 1.47 ± 0.07. Participants with higher MDSs tended to have higher AAC scores [MDS 0: 0.75 (0.56-0.93), MDS 1: 1.02 (0.84-1.21), MDS 2: 2.34 (1.80-2.87), MDS 3: 3.19 (2.46-3.92), MDS ≥4: 4.99 (3.49-6.49)]. Compared with those with an MDS of 0, the highest subgroup (MDS ≥4) was associated with a higher AAC score {ß = 4.24 [95% confidence interval (CI) 2.78-5.70], P < .001} and the association was not altered [ß = 1.81 (95% CI 0.54-3.09), P = .002] after adjusting for numerous covariates. Subgroup analyses showed that stronger associations between the MDS and AAC score were detected in adults with lower levels of magnesium intake and older age (all P for interaction <.05). CONCLUSIONS: The MDS is a promising tool for identifying individuals with magnesium deficiency status who may benefit from dietary magnesium supplementation to reduce the risks of AAC.

Hypomagnesaemia - One Cause To Remember!

A 71-year-old female presented with 5 days of diarrhoea and asthenia. Past medical history of rheumatoid arthritis, arterial hypertension, hypertrophic cardiomyopathy and chronic gastritis was treated with leflunomide, deflazacort, esomeprazole, carvedilol and spironolactone. At admission, the patient's physical examination showed signs of dehydration. Lab results revealed leucocytosis, increased C-reactive protein, hypomagnesaemia, hypocalcaemia and hypokalaemia. A presumption of acute infectious diarrhoea causing hypomagnesaemia with hypocalcaemia and hypokalaemia was made. She was started on ciprofloxacin, IV hydration and electrolyte supplementation with an adequate response. However, magnesium levels fell repeatedly. After excluding other causes for hypomagnesaemia, chronic use of proton pump inhibitors (PPIs) was considered a plausible cause therefore PPI was discontinued, with normalisation of magnesium levels. Hypomagnesaemia is a common disturbance, mainly caused by diarrhoea, gastrointestinal malabsorption, medications, alcoholism and volume expansion. Clinical manifestations include neuromuscular symptoms, cardiovascular manifestations, hypokalaemia and changes in calcium metabolism. PPI-related hypomagnesaemia has been described in later years particularly in chronic use cases, with a medium prevalence of 27%, but further studies remain necessary to clarify its pathophysiologic mechanism. Since PPIs are widely used, it is essential to be aware of hypomagnesaemia as a possible side effect, particularly in refractory cases and after excluding other common causes. LEARNING POINTS: PPIs-related hypomagnesaemia should be a concern, especially in cases with refractory hypomagnesaemia and after excluding other common causes.Formal indication for PPIs use should be revised in most patients.

The complex role of post-operative magnesium on the long term serum calcium and parathyroid hormone levels in patients undergoing total and near-total thyroidectomy.

Objective: To assess the role of hypomagnesaemia in the development of permanent hypocalcaemia following thyroidectomy. METHODS: The prospective cohort study was conducted from April 3, 2017, to January 2, 2020, at Surgical Unit 1, Benazir Bhutto Hospital, Rawalpindi, Pakistan, and comprised of patients of both genders undergoing total and near total thyroidectomy. Post-operative calcium and magnesium levels were noted, and the patients were followed up after 6 months and fasting serum calcium, magnesium and parathyroid hormone levels were checked. Signs and symptoms of hypocalcaemia were noted. Data was analysed using SPSS 22. RESULTS: Out of the 62 patients followed up, 57 (91.9%) were females and 5 (8.1%) males. The overall mean age was 38.5 ± 12.1 years Post-operative hypomagnesaemia was seen in 6(9.8%) patients and none developed follow-up hypocalcaemia. Post-operative magnesium levels were significantly negatively correlated with follow-up parathyroid hormone level (p=0.006). Fall in magnesium post-operatively and follow-up magnesium were positively correlated with follow-up parathyroid hormone (p<0.05). Permanent hypocalcaemia was seen in 7(11.4%) patients and it was significantly associated with pre-operative and post-operative calcium levels, post-operative symptoms of hypocalcaemia and readmission for hypocalcaemia after discharge (p<0.05). Follow-up hypomagnesaemia was significantly associated with follow-up hypocalcaemia (p=0.024) and follow-up symptoms of hypocalcaemia (p=0.031). Conclusion: Acute development of mild hypomagnesaemia post-operatively may be beneficial in early positive feedback for parathyroid hormone secretion. Hypomagnesemia 6 months after surgery may be involved in PTH organ resistance. The complex role of hypomagnesemia on PTH levels must be further explored.

Hypomagnesemia and Poor Glycemic Control among Type 2 Diabetic Patients: A Cross-Sectional Study.

Background/Aim: Hypomagnesaemia has been shown to have a significant impact on both glycaemic control and diabetes complications in type 2 diabetes mellitus (T2DM) patients. This study aims to assess the prevalence of hypomagnesaemia in T2DM patients and find the association between serum magnesium levels and outcomes relevant to glycaemic control and diabetic complications in primary care unit. Methods: A cross-sectional study was conducted and included 373 patients (222 males and 151 females) from primary care unit. Serum magnesium levels were measured by the colorimetric endpoint method using the Cobas C501 system. Hypomagnesaemia was determined to be a serum magnesium level <1.6 mg/dL. In addition, the following data was also obtained: patients' characteristics, anthropometric measurements, smoking status, HbA1c, comorbidities and therapeutic management. Results: Patients' mean age was 56.2 ± 10.8 years, 24.6% were smokers, and most were overweight or obese. About 60% have a history of hypertension, and the majority have had diabetes for more than 10 years. Their mean HbA1c level was 8.5 ± 2%. The prevalence of hypomagnesaemia was 11% (95% CI: 8%-14.6%). It was found to be significantly higher among females (adjusted OR: 2.7, 95%CI: 1.2%-5.8%), patients with HbA1c ≥8% (adjusted OR: 2.4, 95%CI: 1.1%-5.5%) and patients with a history of diabetic retinopathy (adjusted OR: 2.7, 95%CI: 1.1%-7.1%). Conclusion: The study showed that hypomagnesaemia is more prevalent in females and is associated with diabetic retinopathy and poor glycaemic control. Having a sufficient magnesium level may be associated with better glycaemic control and a reduced occurrence of complications.

Clinical presentation and long-term follow-up of dopamine beta hydroxylase deficiency.

Dopamine beta hydroxylase (DBH) deficiency is an extremely rare autosomal recessive disorder with severe orthostatic hypotension, that can be treated with L-threo-3,4-dihydroxyphenylserine (L-DOPS). We aimed to summarize clinical, biochemical, and genetic data of all world-wide reported patients with DBH-deficiency, and to present detailed new data on long-term follow-up of a relatively large Dutch cohort. We retrospectively describe 10 patients from a Dutch cohort and 15 additional patients from the literature. We identified 25 patients (15 females) from 20 families. Ten patients were diagnosed in the Netherlands. Duration of follow-up of Dutch patients ranged from 1 to 21 years (median 13 years). All patients had severe orthostatic hypotension. Severely decreased or absent (nor)epinephrine, and increased dopamine plasma concentrations were found in 24/25 patients. Impaired kidney function and anemia were present in all Dutch patients, hypomagnesaemia in 5 out of 10. Clinically, all patients responded very well to L-DOPS, with marked reduction of orthostatic complaints. However, orthostatic hypotension remained present, and kidney function, anemia, and hypomagnesaemia only partially improved. Plasma norepinephrine increased and became detectable, while epinephrine remained undetectable in most patients. We confirm the core clinical characteristics of DBH-deficiency and the pathognomonic profile of catecholamines in body fluids. Impaired renal function, anemia, and hypomagnesaemia can be part of the clinical presentation. The subjective response to L-DOPS treatment is excellent and sustained, although the neurotransmitter profile in plasma does not normalize completely. Furthermore, orthostatic hypotension as well as renal function, anemia, and hypomagnesaemia improve only partially.

Association of Serum Magnesium with Oxidative Stress in the Pathogenesis of Diabetic Cataract.

Magnesium deficiency enhances oxidative stress which contributes to early development of cataract formation, and also the progression in type 2 diabetes mellitus patients remains unclear. The present study was designed to evaluate the serum levels of magnesium, oxidative stress marker and antioxidant status and to find out if there is any association between them in the pathogenesis of diabetic cataract compared with non-diabetic senile cataract, diabetes without cataract and normal healthy subjects. This comparative study includes 90 type 2 diabetes mellitus patients with cataract, 90 non-diabetic senile cataract patients, 90 type 2 diabetes mellitus without cataract and 90 normal healthy individual subjects without cataract in the age group between 40 and 75 years of both genders. Serum magnesium was estimated by using a fully automated analyser. Serum malondialdehyde (MDA), an indicator of oxidative stress biomarker, was determined by spectrophotometry, and the antioxidant status such as serum reduced glutathione (GSH) and glutathione peroxidase-3(GPX-3) levels was estimated by ELISA method. The present study shows significantly decreased levels of magnesium, GSH, GPX-3 and increased level of MDA in type 2 diabetes mellitus patients with cataract when compared with non-diabetic senile cataract patients, type 2 DM without cataract and normal healthy individuals. A significant negative correlation of serum magnesium with MDA and positive correlation with GPX-3 were observed. The present findings indicate that hypomagnesaemia is a significant pathogenic factor which causes increased oxidative stress which may trigger earlier cataractogenesis in patients with type 2 diabetes mellitus.

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

BACKGROUND: 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. OBJECTIVE: 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). METHODS: 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. RESULTS: 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%. CONCLUSION: In this study, hypomagnesemia was a parameter strongly associated with the diagnosis and progression of T2DM, while FEMg showed no significant association.

Mechanisms coupling sodium and magnesium reabsorption in the distal convoluted tubule of the kidney.

Hypomagnesaemia is a common feature of renal Na+ wasting disorders such as Gitelman and EAST/SeSAME syndrome. These genetic defects specifically affect Na+ reabsorption in the distal convoluted tubule, where Mg2+ reabsorption is tightly regulated. Apical uptake via TRPM6 Mg2+ channels and basolateral Mg2+ extrusion via a putative Na+ -Mg2+ exchanger determines Mg2+ reabsorption in the distal convoluted tubule. However, the mechanisms that explain the high incidence of hypomagnesaemia in patients with Na+ wasting disorders of the distal convoluted tubule are largely unknown. In this review, we describe three potential mechanisms by which Mg2+ reabsorption in the distal convoluted tubule is linked to Na+ reabsorption. First, decreased activity of the thiazide-sensitive Na+ /Cl- cotransporter (NCC) results in shortening of the segment, reducing the Mg2+ reabsorption capacity. Second, the activity of TRPM6 and NCC are determined by common regulatory pathways. Secondary effects of NCC dysregulation such as hormonal imbalance, therefore, might disturb TRPM6 expression. Third, the basolateral membrane potential, maintained by the K+ permeability and Na+ -K+ -ATPase activity, provides the driving force for Na+ and Mg2+ extrusion. Depolarisation of the basolateral membrane potential in Na+ wasting disorders of the distal convoluted tubule may therefore lead to reduced activity of the putative Na+ -Mg2+ exchanger SLC41A1. Elucidating the interconnections between Mg2+ and Na+ transport in the distal convoluted tubule is hampered by the currently available models. Our analysis indicates that the coupling of Na+ and Mg2+ reabsorption may be multifactorial and that advanced experimental models are required to study the molecular mechanisms.

Magnesium biofortification of Italian ryegrass (Lolium multiflorum L.) via agronomy and breeding as a potential way to reduce grass tetany in grazing ruminants.

AIM: Magnesium (Mg) deficiency (known as grass tetany) is a serious metabolic disorder that affects grazing ruminants. We tested whether Mg-fertiliser can increase Mg concentration of Italian ryegrasses (Lolium multiflorum L.) including a cultivar (cv. Bb2067; 'Magnet'), bred to accumulate larger concentrations of Mg. METHODS: Under controlled environment (CE) conditions, three cultivars (cv. Bb2067, cv. Bb2068, cv. RvP) were grown in low-nutrient compost at six fertiliser rates (0-1500 µM MgCl2.6H2O). Under field conditions, the three cultivars in the CE condition and cv. Alamo were grown at two sites, and four rates of MgSO4 fertiliser application rates (0-200 kg ha-1 MgO). Multiple grass cuts were taken over two-years. RESULTS: Grass Mg concentration increased with increasing Mg-fertiliser application rates in all cultivars and conditions. Under field conditions, cv. Bb2067 had 11-73% greater grass Mg concentration and smaller forage tetany index (FTI) than other cultivars across the Mg-fertiliser application rates, sites and cuts. Grass dry matter (DM) yield of cv. Bb2067 was significantly (p < 0.05) smaller than cv. Alamo. The effect of Mg-fertiliser rate on DM yield was not significant (p ≥ 0.05). CONCLUSIONS: Biofortification of grass with Mg through breeding and agronomy can improve the forage Mg concentration for grazing ruminants, even in high-growth spring grass conditions when hypomagnesaemia is most prevalent. Response to agronomic biofortification varied with cultivar, Mg-fertiliser rate, site and weather. The cost:benefit of these approaches and farmer acceptability, and the impact on cattle and sheep grazing on grasses biofortified with Mg requires further investigation.

Diagnóstico de síndrome de Gitelman en paciente con condrocalcinosis / Diagnosis of gitelman syndrome in patient with condrocalcinosis

RESUMEN Introducción: El síndrome de Gitelman es una tubulopatía caracterizada por alcalosis metabólica hipopotasémica, hipomagnesemia e hipocalciuria. Sus efectos musculoesqueléticos son comunes, pudiendo provocar desarrollo de condrocalcinosis. Caso clínico: Paciente con condrocalcinosis de larga data asociada a hipomagnesemia crónica en tratamiento con calcio y magnesio. Tras la suspensión del tratamiento debido a una intervención quirúrgica presentó debilidad generalizada, alcalosis metabólica, hipopotasemia, hipomagnesemia e hipocalciuria con diagnóstico final de síndrome de Gitelman. Tras la instauración de tratamiento, mejoró clínica y analíticamente manteniendo cifras iónicas estables. Discusión y conclusiones: Resulta fundamental un adecuado diagnóstico de este tipo de tubulopatías, ya que un tratamiento adecuado evita complicaciones asociadas.

ABSTRACT Introduction: Gitelman syndrome is a renal tubule disease that involves hypokalaemic metabolic alkalosis, hypomagnesaemia and hypocalciuria. The musculoskeletal effects of Gitelman syndrome are common, including the development of chondrocalcinosis. Clinical case: A female patient with long-standing chondrocalcinosis associated with chronic hypomagnesaemia on treatment with calcium and magnesium. After the suspension of the treatment due to surgery, she presented with a generalised weakness, metabolic alkalosis, hypokalaemia, hypomagnesaemia and hypocalciuria, with final diagnosis of Gitelman syndrome. After re-introducing the treatment, she improved clinically, with electrolytes remaining stable. Discussion and conclusions: A proper diagnosis of this type of tubular diseases is essential because an adequate treatment avoids associated complications.